Challenges of transferring rural adults with chronic HCV infection for further HCV RNA confirmation and free DAAs treatment: a success story of the interdisciplinary collaboration approach

According to the World Health Organization [1], more than 325 million people worldwide are chronically infected with hepatitis B or C virus (HBV or HCV). In many countries, mass infant vaccination has helped control HBV. However, no vaccine has been found to prevent HCV infection [2]. HCV is a blood-borne virus. For some people, it is a short-term illness; for more than 50% of people infected with HCV, however, it is a long-term, chronic infection [2]. Chronic hepatitis C (CHC) is a concern in many countries, and is the leading cause of liver cirrhosis and hepatocellular carcinoma worldwide [3]. CHC, which is defined as being infected with HCV for more than 6 months, is responsible for 57% of cases of liver cirrhosis, 78% of cases of hepatocellular carcinoma, and an estimated 1.3 million preventable deaths a year worldwide [4]. Across the globe, approximately 71 million people are infected with CHC [5]. Research indicates that once a person is infected with HCV, it becomes chronic in 75–85% of cases— with a high probability of progressing to liver cirrhosis and hepatocellular carcinoma [3]. Since the liver has no nerve endings and can function despite 70% of its mass being damaged, liver diseases are commonly referred to as “silent killers” and are often asymptomatic [4, 6].

The average prevalence rate of HCV infection in Taiwan is 3.87% [6]. The rate is even higher (10%) in the country’s southwestern coastal rural areas, making it significantly higher than those in the United States and European countries [1, 7]. This phenomenon was initiated five decades ago when many rural residents of Taiwan were treated with inadequately disinfected medical equipment while sick. For instance, they were given injections by unqualified physicians, which caused many innocent people to be unknowingly infected by HCV [6, 8]. It is estimated that 400,000–700,000 people in Taiwan have CHC. Patients with CHC have been treated with interferon-based therapies, which are commonly associated with adverse effects and long treatment duration [8]. Fortunately, the emergence of direct-acting antiviral (DAA) agents has proven to be a highly effective cure that also maintains patient safety [2, 6, 9‐11]. The Taiwanese government has initiated a national elimination goal of eradicating CHC by 2025, which will be paid for by the Taiwan National Health Insurance (NHI). The free DAAs treatment was launched in 2017, with a maximum of around 11,000 treatments being provided annually, and each treatment costing 10,000 USD [6, 12].

Previous studies have indicated that universal HCV screening for adults, rather than just for birth cohorts and high-risk populations, is a key intervention tool used to inform people of their hepatitis status, and direct and motivate those infected to obtain the necessary medical care [4, 13, 14]. Given the costs, there are usually two steps to screen and confirm for an active HCV infection. The first step is to encourage people to participate in blood screening for anti-HCV; this is because being serum anti-HCV positive indicates either an active or a resolved HCV infection. If this test is positive, a confirmatory test—the HCV ribonucleic acid (RNA) test, also known as the HCV viral load test—is performed in order to identify active CHC infection [1, 15].

Although evidence indicates that DAA treatment for HCV has been successful, involves few side effects, and is free of charge through Taiwan’s NHI [6, 8], many people with HCV do not have sufficient knowledge regarding liver health and treatment. For instance, Lin et al. [4] found that people who underwent blood screening for anti-HCV did not know the results nor their hepatitis status. Indeed, there is a gap that needs to be addressed in order to achieve the national elimination goal of eradicating HCV [4, 14, 16]. In this regard, primary healthcare providers—who work at the frontline of the healthcare system—play an important role in actively promoting the free DAAs policy of the Taiwanese government. They should refer people with chronic HCV infections in rural areas for transfer to a qualified hospital for HCV RNA confirmation and free DAAs treatment. The aim of this study is to explore the implementation facilitators of and barriers to inviting potentially infected chronic HCV patients in rural areas to accept transfers for HCV RNA confirmation, and encouraging those who are HCV RNA positive to avail of free DAAs treatment.

Of the 1795 adults who were serum anti-HCV positive according to the medical records of the collaborating hospital and clinics, 1149 (64%) accepted a transfer to the hospital for HCV confirmation; among the 1149 patients who accepted transfer, 623 (54.2%) were identified as being HCV RNA-positive (Fig. 2). Among them, 552 (88.6%) were willing to undergo DAAs treatment for 2–3 months at the collaborating hospital, while 71 (11.4%) were hesitant to do so (Fig. 3).

The finding shows the facilitators of the participants’ willingness to be transferred in relation to the four main points communicated during the telephone interview: (a) the research team used “treatment is provided for free” to convince participants to accept the hospital referral since some residents had previously undergone treatment with interferon-based injections and experienced a lot of painful side effects because of it. Further, participants were introduced to the free oral medication (DAAs), which had a nearly 100% cure rate and relatively little side effects. A patient qualified for DAAs treatment can save up to 300,000 Taiwanese dollars (TWD) (equivalent to 10,000 USD). Many participants were happy because of this talk. Later, (b) “full understanding of the mechanism of HCV” was explained to the participants. For example, keeping in mind their health-related knowledge and social status, the participants were informed that a “virus like a worm” lives inside their body (liver). However, the virus cannot be easily detected as is it is asymptomatic and is very small; hence, the “worm” needs to be killed or “thrown out of the garden.” During this step, many participants responded that they could understand the mechanism of HCV because of this talk.

Regarding (c) “let us join the national goal and take part in eradicating HCV,” the participants were informed that the government initiated a free program. However, there are limitations as to the number of treatments provided yearly. Thus, the earlier the hepatitis is confirmed, the earlier treatment can be started; otherwise, it will be delayed to the next year. Many participants felt anxious during this step and reported barriers to their receipt of treatment. Regarding (d) “reducing transfer or treatment barriers,” many rural residents mentioned that they faced barriers when transferring to another hospital, such as unfamiliarity with the hospital and transportation problems. The research team assured the participants that there would be someone waiting for them at the gate of the hospital, and that a volunteer (such as a village leader or nursing student) would guide them through each process at the hospital. In addition, the participants were informed that after they began the treatment, the research team would follow up on their response to the drugs. Many participants were reassured by this and immediately said yes.

Table 1 shows the barriers experienced by the 646 participants who did not confirm their treatment; 297 (46%) participants directly refused to be transferred, while 349 (54%) had an invalid telephone number, did not answer, or were dead or hospitalized. Among the 297 patients who refused confirmation, the top four barriers were as follows: (a) the self-perception that they were healthy (n = 98; 32.3%) (e.g., “I don’t feel any discomfort at all! There is no need to see doctors! Just save the medical resources for others,” “My liver doesn’t feel painful, and I also need to work every day, so I don’t have spare time to see doctors,” “I don’t think there is a need for me to see doctors; I do not know what hepatitis C is,” “I don’t feel any discomfort on a daily basis; it’s really weird to take medicines for no reason”; (b) mistrust of treatment/healthcare ((n = 60; 20.2%) (e.g., “I am used to taking Chinese medicines instead of Western ones; I trust Chinese medicines more than Western ones”); (c) transportation issues (n = 52; 17.5%) (e.g., “I did not go to school when I was young; I don’t even know how to take a shuttle bus to the hospital,” and “The hospital is far away from my home … it always takes me at least 2 hours to go see a doctor … without my children’s help, it’s impossible for me to go to the hospital alone”); and (d) work conflict (n = 30; 10.1%) (e.g., “I need to work for my whole family; I have 3 work shifts,” “It’s impossible for me to take any time out to see a doctor; just wait and see … ,” “I’m more worried about being jobless than having hepatitis,” and “Without a job, I cannot afford a good life for my family”).

Although previous research has indicated that oral DAAs have a high cure rate over a short duration, have few side effects, and are free, many potential HCV patients still face barriers to viral detection and being referred for DAA treatment [5, 6, 17]. Therefore, the present study aimed to understand the implementation facilitators of and barriers to inviting potentially infected patients to accept transfer to a hospital for HCV RNA confirmation and free DAAs treatment in the western coastal Yunlin County [8]. Three key findings emerged from this study. First, it was an efficient strategy to use the anti-HCV data from the collaborating hospital’s medical records for case-finding and to work with the collaborating hospital and clinics. Second, a nurse-led interdisciplinary collaboration involving five elements of referral and a telephone interview with four points for communication significantly facilitated the transfer of potential CHC patients to a hospital and increased their willingness to undergo DAAs treatment. Third, barriers to being referred to a hospital included a high percentage of patients who were unable to be contacted, the patients’ self-perception of being healthy, mistrust of treatment/healthcare, transportation issues, and work conflict.

Recently, in Australia, Pourmarzi et al. [18] demonstrated that a key to achieving the HCV elimination goal is the provision of its treatment in community settings, and that the integration and coordination of care and support provided for both patients and healthcare providers are important processes. The present study lends support to Pourmarzi et al. [18], who reported that successful elements of treatment in community settings include “training and support for healthcare providers, an open referral policy, linkage with or providing outreach services, a person-centered approach, and on-site screening and assessment.” Further, to increase access to treatment for HCV in Australia, White et al. [19] developed a community-based FibroScan and a nurse-led service to assess patients. All patients had treatment prescribed and monitored in primary care, and a telephone follow-up was conducted to confirm that sustained virologic response (SVR) was performed by a clinic nurse. They found that the community-based model facilitates access to HCV treatment in primary care with excellent SVR rates. In Taiwan, the confirmation of HCV and prescription of DAA still requires specialty physicians. The authors of this study strongly recommend that community nurses or primary healthcare providers initiate an integrative program to increase public awareness and promote the referral system for HCV screening and treatment. For instance, there are 368 district public health centers in Taiwan, each with a mastery of the local population’s annual health screening data. If these public institutions could duplicate the present study protocol—wherein once HCV RNA positivity was confirmed by the public health center, the patient would be persuaded to accept free DAAs treatment for 8 ~ 12 weeks depending on his or her genotype—mobilizing such efforts to actively promote DAAs treatment would be an effective integrative program to eliminate HCV in Taiwan.

Unfortunately, many residents with anti-HCV refused to be referred to a hospital for further confirmation because they perceived themselves to be healthy, and appear to have no uncomfortable symptoms. This finding is similar to that of Cheng et al. [20], who conducted a study in remote southern Taiwan. They stated that less than half of confirmed HCV-infected residents received adequate medical care. In addition, Treloar and her colleagues [16] described barriers to HCV care and stigmatization from a social perspective. Previous studies have emphasized the relationship between stigma and adverse health outcomes as well as health access measures. Stigma is a defining factor in HCV treatment, given the association of HCV with the socially demonized practice of injection drug use [16, 21]. Although the present study did not explore the effect of stigma on hospital transfers, it is necessary to comprehensively understand why some people refuse to be referred to a hospital. Nonetheless, when the present researchers approached the residents, some responded that they are worried about the phone scam gang, while others reported having transportation issues or not having enough time because of their need to keep working.

Regarding the barriers of hospital transfer, for rural residents, the hospital is 40–60 km away from the village, and it is particularly difficult for elders to get to without transportation assistance. In addition, it was hard for our research team to reach most patients to notify them because they do not have correct telephone numbers and many residents do not care about DAAs treatment because they feel healthy. Thus, the barriers to being referred to a hospital were clarified. The research team emphasized the communication of the following points to the anti-HCV positive villagers: (1) Since the Taiwanese government fully subsidizes DAAs treatment, patients should seize the opportunity to avail of the free treatment before the annual limit is reached; (2) health is priceless and is the most worthy investment; the sooner you complete your DAAs treatment, the sooner you can rid yourself of the threat of liver cancer; (3) with regard to the 552 patients concerned about adopting the treatment, appropriate health education was given as well as regular reminders to take their medicine; (4) weekly calls were made to remind the patients to return to the hospital for treatment completion; and (5) those who experienced excellent results after undergoing the DAAs treatment were encouraged to promote acceptance of treatment among other patients.

This study has some limitations that should be noted. First, although the research team encouraged all healthcare providers in the outpatient clinics to survey medical records and refer each anti-HCV patient to the collaborating hospital for HCV confirmation, some medical personnel from the private sector had reservations regarding this approach (e.g., some of them felt that it was not so important). In addition, there were no incentives for primary healthcare providers from public health centers to make transfer referrals. Consequently, this may limit the case findings from rural areas. Second, the high percentage of invalid telephone numbers and failure to answer the telephone limits the referrals and the effectivity of the approach used in the study. Thus, it is necessary to reestablish valid telephone connections via the public and private sectors. Third, Taiwan has launched the NHI system and covers almost all of the Taiwanese population. However, since each item for the antibody test costs less than 7 USD, while each HCV RNA confirmation costs over 70 USD, the government uses two steps to confirm an active HCV infection. This procedure increases the barriers to hospital transfer for HCV RNA confirmation and DAAs treatment of CHC patients. Therefore, we strongly suggest that confirmatory testing (HCV RNA) should be done locally, with referrals for those that are HCV RNA positive.

The findings of this study show that the interdisciplinary collaboration approach, with five elements of referral and a telephone interview wherein four points for communication are emphasized, significantly influenced the patients’ acceptance of hospital referrals and their willingness to undergo a new drug treatment in endemic rural areas of Taiwan. In addition, it was an efficient strategy to use medical records provided by the collaborating hospital, clinics, and district health centers to identify residents who were anti-HCV positive and increase case findings. Future research should focus on reducing barriers to hospital transfer and treatment in disadvantaged areas, such as transportation issues, work shifts, invalid telephone numbers, and incorrect self-perceptions of being healthy.