Eligibility criteria

Two investigators (DM and JEF) selected potentially relevant studies for data extraction in accordance with the PRISMA guidelines, set for populations of people living with viral hepatitis and/or cirrhosis. The inclusion criteria were as follows: 1) qualitative and quantitative studies exploring barriers and enablers of HCC surveillance, and 2) qualitative and quantitative studies exploring barriers and enablers of care for patients with cirrhosis and/or viral hepatitis. Studies included surveys, focus groups, and interviews with patients, clinicians, or both. Only quantitative studies that included qualitative or open-ended questions and self-expressed free text written or oral responses in surveys were included, and only data from these responses were included in the study.

Search strategy

An Ovid search was performed using MEDLINE and APA PsycInfo databases using key term combinations of cancer and cirrhosis terms (“liver cirrhosis”, “viral hepatitis”, “hepatitis B”, “hepatitis C”, “liver cancer”), barriers and enabler terms (“surveillance”, “barriers”, “non-adherence”, “limitation”, “refusal”, “patient acceptance of health care”, “patient compliance”, “treatment refusal”, “cultural diversity”) and outcome terms (“hepatocellular carcinoma”, “improve”, “increase uptake”, “adherence”, “improvement”). The dates searched were from January 1, 2012, to August 10, 2023. Articles written in languages other than English were excluded. A PRISMA flow diagram of the search results is shown in Fig 1.

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Fig 1. PRISMA flow diagram of paper identification, review, inclusion and exclusion.

https://doi.org/10.1371/journal.pone.0313216.g001

Extraction

Study characteristics and outcome data were extracted and assessed independently by two reviewers (DM and JEF) using Covidence—Version 2.0 and a standardized form in Microsoft Word. The main components of the assessment were the inclusion and selection of studies, and reporting of study characteristics and outcomes. Data and variables extracted included authors, study years, countries, cohort size, aetiology of liver disease, study methods, study results and quality appraisal.

Quality appraisal and risk of bias

The Critical Appraisal Skills Programme (CASP) checklist was used by both reviewers to assess the quality of each study and the risk of bias [22]. The studies included have moderate to high risk of bias, and for the purpose of this review, we decided to use a narrative method to report the studies. After removing the high risk of bias studies, there was no discernible difference in the results. Thus, it was decided to report on all these studies for the purpose of this review.

Knowledge of liver cancer and HCC surveillance

Several studies from Asia-Pacific region countries with well-established HCC surveillance programs have explored the impact of knowledge and awareness on HCC surveillance uptake. A survey study by Chen and colleagues conducted in a single medical institution in Taiwan recruited 400 patients living with chronic hepatitis B and/or hepatitis C and explored patients’ perspectives on HCC prevention [24]. Responses from the survey indicated that patient knowledge about HCC prevention was closely associated with age, education level, household income and knowledge of viral hepatitis. The study recommended detailed communication and education from healthcare providers regarding viral hepatitis related HCC as essential to prevent or detect HCC early, especially in elderly individuals and people from low socioeconomic backgrounds and education levels who had lower HCC knowledge.

Two studies from China reported knowledge barriers to HCC surveillance [25, 26]. A survey of 352 patients with chronic hepatitis B and/or hepatitis C from hospital outpatient clinics investigated HCC surveillance practices and the association of sociodemographic factors with surveillance knowledge and uptake [25]. Factors associated with better knowledge and likelihood of HCC surveillance uptake included greater knowledge of viral hepatitis and cancer surveillance guidelines, with patients with high school or college younger patients having higher levels of knowledge being more likely to undergo routine screening. Household income and insurance status did not impact surveillance knowledge or uptake by patients, however participants living in rural provinces reported less knowledge of hepatitis B and liver cancer than those living in urban provinces. The study demonstrated a deficiency in HCC surveillance awareness among patients, with many undergoing AFP surveillance simply because they were asked to do so by their doctors without understanding why. While the study noted that physicians in China are often regarded as authoritative figures, and it is essential for clinicians to specifically recommend HCC surveillance to patients to increase uptake, many participants stated that this recommendation to undergo HCC surveillance has not been made by their physicians.

Furthermore, Dai et al. conducted a study involving 380 patients with chronic liver disease in China, aiming to identify sociodemographic, clinical, and psychological factors influencing HCC-related knowledge [26]. Responses to this survey showed that patients with a college education or above and those with a longer duration from diagnosis of chronic liver disease had better knowledge of HCC including surveillance, possibly due to more frequent clinical visits, thereby increasing opportunities for patients to be exposed to HCC education.

In Australia, Sheppard-Law et al. surveyed 177 patients living with hepatitis B across three tertiary hospital clinics, aiming to investigate the factors associated with HCC surveillance [27]. Participants’ country of birth according to WHO region was Western Pacific (78%), Africa (8.4%), Europe (5.1%), and South East Asia (8.5%). Patients in this study were more likely to uptake HCC surveillance if they had higher levels of knowledge and awareness of the importance of six-monthly surveillance, which was associated with pre-hepatitis B treatment education, longer duration of therapy, and attendance at a hepatology specialist clinic. Interestingly, participants who reported a family history of HCC were less likely to be aware that six monthly screening was recommended.

Another Australian study by Allard et al explored African-born Australians’ understanding of HCC surveillance and the risks associated with chronic hepatitis B using semi-structured interviews conducted with 19 patients recruited from a hospital and three recruited from community clinics [28]. Participants mostly understood the significance of the impact of hepatitis B on the liver and reported that the risk of liver cancer was high, particularly among people who had known someone who had died from this cancer. Moreover, younger patients cited liver problems as “associated with aging” and the relationship between regular HCC surveillance to reduce the risk of liver cancer death was generally not understood, highlighting that lack of knowledge were major barriers to HCC surveillance uptake in this key population.

Several studies have been conducted in the USA exploring factors impacting HCC surveillance uptake. Li et al. conducted a phone survey with 467 patients with chronic liver disease attending a single tertiary hospital liver clinic in St Louis, USA. This study aimed to identify barriers and enablers of HCC screening. The study compared HCC screening awareness with colorectal, prostate, and breast cancer screening awareness in patients with chronic liver disease. Of patients with liver disease, 79% reported that they were aware of liver cancer screening. Patients with higher education, no alcohol use in the past year, and a cirrhotic liver were more likely to know about liver cancer screening. Fifty percent of patients reported that their doctors had talked to them about liver cancer, with the prevalence of doctor-patient communication not differing by sex, age, BMI, smoking status, alcohol usage, or frequency of doctor visits. However, Caucasians, patients with higher education levels, and those with cirrhotic livers were more likely to remember their doctor talking to them about liver cancer [29]. Also in the USA, Farvardin et al. conducted a study of 541 patients living with cirrhosis, aiming to identify patient-level knowledge and barriers to HCC surveillance uptake and their association with receipt of HCC surveillance in an ethnically diverse and socioeconomically disadvantaged cohort of 541 participants from Dallas County [30]. Factors associated with higher levels of overall knowledge included being Caucasian, English as a primary language, hepatitis C-related cirrhosis, receiving specialist care, higher educational attainment, and high perceived likelihood of dying from HCC, while factors associated with lower levels of knowledge included living alone, and lack of insurance.

Traditional health beliefs, culture, stigma and discrimination impacts on HCC surveillance uptake

Traditional health beliefs and stigma can impact HCC surveillance uptake and have been directly explored in some studies. For example, discrimination against people with hepatitis B, health beliefs and culture in China are identified as barriers to HCC surveillance uptake, with stigma linked in part to myths surrounding how hepatitis B is transmitted and reducing the willingness of people with hepatitis B to disclose their infection status, access health services for their infection, or undergo HCC surveillance [25, 26, 31]. A survey study conducted by Dai et al. showed that patients with a greater trust in doctors had greater levels of knowledge of HCC risks and surveillance [31]. Main themes in barriers to surveillance reported by 23 hepatitis B patients included their capacity to endure physical suffering, family priorities and responsibilities, and the lack of support from the community, health systems and policies.

In the Australian study by Allard et al, diagnosis of HCC was described as a major life event with significant psychosocial ramifications [28]. Due to limited knowledge of chronic hepatitis B among the African community in Melbourne, confusion with HIV/AIDS, and related stigma experienced within the community, a diagnosis of HCC or uptake of HCC surveillance was perceived as potentially leading to community exclusion and negative experiences in healthcare, employment, and educational settings. Most participants were unaware that social exclusion related to blood borne infections infringed human rights and were unaware that disclosure of viral status was only mandatory in limited situations. Some older patients accepted the diagnosis by understanding that hepatitis B was common in their family and community, while younger patients were more likely to self-stigmatize when they did not know others living with chronic liver disease. Additionally, when it came to intimate relationships, it was reported that disclosure was sometimes associated with the risk of being questioned about fidelity and its related impact on their relationships, in part due to the risk for HCC being related to hepatitis B as being understood as a sexually transmitted infection. While these studies have limited samples from specific communities that cannot be generalised more broadly, they highlight the impact stigma and community perceptions can have on HCC surveillance uptake among at-risk populations.

Logistical barriers

Logistical and health system barriers to HCC surveillance uptake differ significantly between countries, however they remain commonly cited barriers to HCC surveillance uptake by patients and clinicians in both low and high resource settings.

Two studies from the United States highlighted significant logistical barriers to HCC surveillance, delivery, and uptake. Farvardin et al. highlighted the main barriers to HCC surveillance uptake experienced by patients being difficulty in scheduling liver ultrasound appointments, out-of-pocket cost to patients of HCC surveillance tests, uncertainty of where to access HCC surveillance, and difficulties with transportation. At least one of these barriers was reported by half of respondents, while 23% reported several barriers. Less commonly reported barriers included fear of poor surveillance test efficacy, fear of finding cancer, the time commitment required to attend surveillance, and fear of pain from surveillance tests [30].

Singal et al. conducted a telephone survey of 1020 patients living with cirrhosis within three different health systems in the USA, to characterize patient knowledge, attitudes, and barriers to HCC surveillance and their association with surveillance uptake in a racially and socioeconomically diverse cohort of patients. Similarly, nearly half of the patients in this study reported logistical barriers to HCC surveillance, including cost, scheduling, and transportation [32].

Similar logistical barriers to HCC surveillance have been reported in Asian countries. In China, Xu et al. surveyed 352 patients with chronic hepatitis B and/or hepatitis C from hospital outpatient clinics. They found patient-perceived logistical barriers to HCC surveillance included lack of time, difficulty accessing medical facilities and fear of cancer detection [25]. A survey study from Thailand where the universal medical coverage scheme supports HCC surveillance to all patients with high-risk liver disease, found that financial concerns were not a significant barrier to surveillance uptake. However, the lack of ultrasounds being requested by physicians was associated with a low rate of HCC surveillance uptake, reflecting health systems barriers in busy hospital settings [33].

Knowledge of liver cancer and HCC surveillance

Studies among primary care physicians in the USA described lack of knowledge being the key barrier to implementing surveillance for their patients. In a study in New York, Han et al. examined barriers and enablers to care for patients with viral hepatitis from the perspective of ethnically diverse primary care physicians through semi-structured interviews. The primary care physicians self-identified as being of Korean, Chinese, Egyptian, or Russian ethnicity, fluent in their native language, with 65% of their patients being of the same cultural and language background. Some reported barriers to care included busy patients and doctors, miscommunication and language, cultural beliefs, healthcare costs, lack of patient and provider knowledge, and lack of community-based viral hepatitis surveillance initiatives to identify those at potential risk for HCC. Alternatively, some of the facilitators of care identified included fear of illness, preference for follow-up with physicians within the community, community support, engagement of primary care physicians for specialty care, and insurance status [34]. Furthermore, McGowan et al aimed to understand North Carolina primary care providers’ knowledge and practice of HCC surveillance via a survey with the results showing only 45% who see cirrhosis patients recommend surveillance and of those, only 70% did so because they believe evidence supports it. Of the primary care providers who did not conduct HCC surveillance, 84% referred to specialists to provide surveillance and 24% were unaware of surveillance recommendations. Only 8% did not provide HCC surveillance due to lack of belief in a survival benefit [35].

Inconsistent guidelines

A survey of 109 primary care physicians in New York treating immigrants from countries with endemic viral hepatitis described several HCC practices and barriers [36]. HCC surveillance for hepatitis B patients was recommended by just over two-thirds of the 93 providers responding to that question. Of 85 respondents, 78% determined that HCC surveillance should be performed for immigrant patients from high-risk regions living with hepatitis B, even if no symptoms are present while over half of the providers stated that there was a lack of clear HCC surveillance guidelines, while a further proportion expressed lack of clarity in existing HCC surveillance guidelines for which groups should receive surveillance. Even though most providers identified that ultrasound should be used for surveillance, only 64% stated that it should be performed every 6 to 12 months. Moreover, a web-based survey from Australia, explored provider- and practice-level factors associated with guideline-consistent recommendations for HCC surveillance in patients with cirrhosis among 131 primary care physicians. Barriers to surveillance included misconceptions about how best to perform surveillance, perceived and experienced difficulties in effectively implementing surveillance, not being up-to-date with current HCC surveillance guidelines, and not receiving systems-level reminders, such as computer-based prompts for HCC surveillance. In contrast to guideline recommendations for 6 monthly liver ultrasounds, 90% of respondents interviewed believed alpha fetoprotein (AFP) was an effective surveillance test when used alone, with two-thirds reporting performing annual instead of biannual HCC surveillance. Most respondents believed that computerized tomography (CT) and Magnetic Resonance Imaging (MRI) were effective as HCC surveillance tests, and one-fourth of the providers reported using CT/MRI intermittently as surveillance tests in their patients instead of liver ultrasound. Thus, several HCC surveillance recommendations and practices reported by primary care physicians are inconsistent with current guidelines [37].

In an additional study from the USA, Mukhtar et al. aimed to describe primary care physicians’ knowledge of and barriers to the management of hepatitis B in a culturally diverse patient cohort across several healthcare systems in San Francisco. This was done via a mail survey with 277 primary care physicians participating (41.3% response rate). Major barriers included unfamiliarity with and lack of clarity of hepatitis B management guidelines and HCC surveillance, and a lack of awareness of when hepatitis B should be treated or understanding that hepatitis B-induced liver cancer can occur in the absence of cirrhosis. Furthermore, although most providers performed HCC surveillance, only half performed HCC surveillance in >75% of hepatitis B patients [38]. Simmons et al. explored the knowledge and barriers to HCC surveillance among primary care physicians at university-affiliated academic medical centres in the USA via an electronic survey. Barriers to HCC surveillance in the study included limited time in the clinic, competing clinical concerns, and not being aware of current surveillance guidelines [39]. Barriers to HCC surveillance were evident among medical graduates. Mahfouz et al. surveyed medical trainees from three different institutions in Miami to evaluate the knowledge of perspectives on barriers and facilitators for surveillance for hepatitis B and HCC. Barriers cited by participants included lack of clarity in HCC guidelines (46.7%), lack of awareness about HCC guidelines (39.6%), and patient financial barriers (28.6%), with only 16.5% responding that there were no barriers to HCC surveillance. On the other hand, some respondents were highly likely to screen for HCC if evidence strongly suggested that surveillance leads to decreased mortality (95% agree/strongly agree) or if surveillance was recommended by a national organization (87% agree/strongly agree) [40]. This study highlights the importance of adequate education for medical trainees to facilitate HCC surveillance delivery once they independently practice medicine.

Specialists expressed similar issues to primary care providers, in that unclear and inconsistent guidelines reduced HCC surveillance uptake. Kim et al. surveyed 654 gastroenterology and hepatology providers from 26 medical centres in 17 U.S. states, of whom 305 completed the survey (47% response rate). The survey sought to assess existing HCC surveillance practices and investigate whether decisions to screen patients for HCC and their choice of surveillance test were influenced by patient-specific HCC risk. Barriers to surveillance include limited clinical time and patients’ costs of care, transportation, and scheduling. There were significant differences in HCC surveillance recommendations by healthcare provider type: trainees were more likely to order ultrasound alone, whereas experienced providers were more likely to order cross-sectional imaging and surveillance for patients with annual HCC risks of 0.1% and 0.5%. The reasons for these findings may include incomplete awareness of guidelines, trainee modelling after the practices of their faculty physicians, and experienced providers being more concerned about missing HCC and related legal ramifications in the American health system, prompting more aggressive surveillance, while the availability of HCC-related guidelines was an important facilitator of surveillance [41]. Another mixed methods study, including a qualitative (semi-structured interviews) component followed by online survey among 214 healthcare providers in the USA aimed to understand HCC care challenges. Healthcare providers included oncologists, hepatologists, oncology physician assistants, oncology nurse practitioners, and interventional radiologists that were involved in HCC care. The main barriers to HCC surveillance that were reported included adherence to established surveillance criteria, use of appropriate imaging for diagnosis and making the decision to perform a diagnostic biopsy [42].

In Canada, an online survey among 71 members of the Canadian Association for the Study of the Liver, most being gastroenterology and hepatology providers, was conducted to understand their HCC surveillance practices and barriers among patients living with chronic hepatitis B [43]. The survey results showed significant differences and inconsistency in surveillance practices and in following guidelines. The main barriers reported included patient non-compliance, a lack of an automated recall system and limited access to ultrasound machine or MRIs.

Logistical barriers

In the Asia Pacific region, the main barrier to HCC surveillance perceived among physicians in Mongolia included cost and the inability of patients to pay for diagnostic tests, with other barriers cited included the of lack of clinical guidelines and poor patient awareness [44]. A survey conducted among physicians in Thailand showed that more than half failed to suggest proper surveillance to patients at risk for HCC, despite most believing that HCC surveillance was a shared responsibility by all healthcare providers and that it was cost-effective. The survey results highlighted that some of the barriers to screening was a lack of knowledge regarding intervals of HCC surveillance, limited access to ultrasound machines especially in rural areas and that the AFP test was unavailable in over 70% of community hospitals [33].

Conclusions

Our systematic review of qualitative studies highlighted several key barriers to HCC surveillance uptake as perceived by both patients and clinicians, including lack of knowledge, conflicting guidelines and logistical barriers. Further qualitative studies representing greater diversity among participants from different health system and resource contexts are needed to better inform design of effective HCC surveillance programs and health promotion strategies.