Effect of an Active Reach-Out Program on Hepatitis C Screening Test for Drug-Addicted Inmates in Southern Taiwan ^†

Abstract

Chronic hepatitis C is an important threat to the world’s public health. In Taiwan, 2~4% of the population is infected with hepatitis C, and 10~15% of those cases will lead to liver cirrhosis. This study examined the effect of a comprehensive screening test project conducted by the Addiction Treatment Center in southern Taiwan. In collaboration with the Drug Addiction Treatment Center, 154 screening tests were completed. It is demonstrated that through active reach-out screening service with innovative process design, the vulnerable groups of people with a potentially high prevalence of HCV could be targeted and cured. Nevertheless, close surveillance and follow-up would be necessary to prevent the reoccurrence.

1. Introduction

According to the statistics of the Ministry of Health and Welfare, Taiwan, cancer ranks first among the top ten causes of death, and liver cancer ranks second among the top ten cancers [1]. The statistical results show that hepatitis, liver cirrhosis, liver cancer, and other diseases are seriously threatening the lives and health of Taiwanese people.

Hepatitis C is contracted through blood transfusion and is mainly characterized by long-term chronic symptoms. It is estimated that the global prevalence of hepatitis C is about 2.8%, while the prevalence rate in Taiwan is 3.28% [2]. A further analysis shows that the prevalence rates could reach 15% or even higher in certain towns or villages in the southwest area.

In terms of the development process of hepatitis C virus infection, about 70% to 80% of the patients who suffer from acute hepatitis C will develop into chronic hepatitis C, and among the patients with chronic hepatitis C, nearly 20% may turn into liver cirrhosis in 20 years. Those cirrhotic hepatitis C patients have a 1–4% chance of developing hepatocellular carcinoma and a 4–5% chance of liver function decompensation each year, which may result in considerable subsequent treatment costs [3]. Based on the 2020 National Health Insurance Administration statistics for the medical expenditures of cancer-related inpatient/outpatient health services, the number of outpatient visits for cancer was 181,000, and the annual health expenditure was about NTW 22.33 billion, all indicating that the financial burden for cancer care becomes an important issue and cannot be underestimated.

In September 2015, the World Health Organization (WHO) convened the World Hepatitis Summit in Glasgow, Scotland, at which a “Glasgow Declaration on Viral Hepatitis” was drawn up on the prevention and treatment of hepatitis. It was declared that universal access to the prevention, diagnosis, care, and treatment of viral hepatitis is a fundamental human right, and, therefore, calls on governments to work with all stakeholders, including non-profit organizations, medical professionals, and pharmaceutical companies, to develop and implement comprehensive hepatitis funding programs dedicated to eliminating this significant public health threat. The Declaration clearly highlights the goal of eliminating the threat of hepatitis C by 2030 [4].

Taiwan is one of the few countries in the world where the prevalence of hepatitis C exceeds 3%, much higher than that of other Asian neighboring countries such as Japan (0.98%) and South Korea (1.2%). Therefore, it becomes an urgent issue for the authorities in Taiwan to launch necessary healthcare strategies for the prevention and treatment of hepatitis C. In order to achieve the goal of eliminating hepatitis C by 2025 [5,6,7], the National Hepatitis C Elimination Office was established in 2016 to initiate the “National Hepatitis C Elimination Policy Program 2018–2025 (referred to as the Policy Program)”. It was expected that a target of 250,000 people treated with direct-acting antiviral agent (DAA) for hepatitis C would be reached by 2025, and a core strategy and policy direction for hepatitis C elimination would be generated [8].

Among all the drug addicts who suffer from hepatitis C, the inmates in drug rehabilitation institutions are usually underprivileged groups of people. Therefore, the new cases of hepatitis C infection in Taiwan are mainly intravenous drug addicts or people with a higher risk of infection, especially younger males. In view of this, the subject hospital (a government-affiliated region-level hospital in southern Taiwan) undertook the responsibility of caring for the vulnerable people in the rural areas. To put this in practice, they took the initiative to ask the authorities, the Central Health Insurance Administration, for assistance in diagnosis and treatment to ensure patient safety.

2. Literature Review

2.1. Introduction to Hepatitis C

Hepatitis C virus is mainly transmitted through blood or body fluids. The transfusion of blood or plasma products is a well-known transmission route. In the United States, the incidence of infection due to blood transfusion is about 6%, but it could reach up to 42% with intravenous drug use. Other possible transmission channels include sexual behavior (6%), family contact (3%), medical issues (2%), and dialysis (0.6%). In Taiwan, the prevalence of serum antibodies of hepatitis C among family members is about 5.4%, while the positive rate of spouses’ antibodies is 21%. It is, thus, suspected that prolonged contact may be the main cause of mutual infection between spouses. Pregnant women with risk factors (such as HIV infection) will affect the virus concentration, making the newborns more susceptible to hepatitis C virus infection, and they become chronic carriers, as defined by a detectable existence of HCV RNA in the blood of the patient for more than six months.

About 20–40% of people who are infected with hepatitis C can clear the virus on their own at the initial stage, and the rest will develop into chronic hepatitis C, some of whom may gradually deteriorate into liver cirrhosis or liver cancer within 40 years [4]. Clinically, the production efficiency of the hepatitis C virus in the human body is very high, and the copied gene body can often undergo mutations. Therefore, the virus in patients is seldom of a single species but a collection of many different mixed virus groups. This phenomenon may be related to the immune response of virus escape from the host. About 80% of people infected with hepatitis C will develop a chronic infection, and the speed of disease progression is influenced by certain factors such as age and gender. For example, among women or young infected people, the disease progression is relatively slow. It usually takes about 30 years to develop into chronic hepatitis C. However, for those who are male, older, alcoholic, or co-infected with hepatitis B or HIV, progressing into cirrhosis may be completed within 20 years, and there is a 1–5% chance of developing liver cancer after the occurrence of cirrhosis [3].

Hepatitis C virus genotype (HCV Genotype) can be classified into 1a, 1b, 2, 3, 4, 5, 6 and other types. Each genotype of the hepatitis C virus needs a different treatment. The treatment courses and therapeutic effects are different as well. Before using drugs to treat hepatitis C, the degree of liver fibrosis (hepatic fibrosis) must be diagnosed with abdominal ultrasonography. Based on the Metavir score, the diagnosis falls into one of the following five stages: F0 (normal liver tissue, without fibrosis), F1 (mild fibrosis, fibrosis limited to the hepatic portal area, no septum), F2 (moderate fibrosis, a few fiber bundles protrude from the hepatic hilar area to the lobules, with a few septa), F3 (severe fibrosis, many fiber bundles protrude from the hepatic hilar area to the lobules, with many septa), and F4 (severe fibrosis, fibrous tissue coherent and formed a circle, which can be diagnosed as liver cirrhosis) [9,10].

If the hepatitis C (Anti-HCV) antibody is detected positive, it means that the patient has been infected with the hepatitis C virus. Sometimes, the virus may not be detected in the blood because the hepatitis C antibody in the blood may continue to be positive for many years. Anyway, when the hepatitis C (Anti-HCV) antibody is positive, the patient needs to be referred to a medical institution for further testing of hepatitis C virus ribonucleic acid (HCV-RNA) and hepatitis C virus genotype (HCV Genotype). A positive test result for hepatitis C virus ribonucleic acid (HCV-RNA) indicates that the virus has been detected in the blood. The value of this test can be used to assess whether treatment should be given and the possible effect of treatment [9,10].

2.2. Status Quo in Taiwan

The prevalence rate of anti-hepatitis C virus antibodies in Taiwan is about 3.28% [2]. It is, thus, estimated that about 740,000 people have been infected with the hepatitis C virus, of which 550,000 people might develop chronic hepatitis C. The prevalence rates in certain townships in southwestern Taiwan could even reach 15% or higher, such as 38% of adults in Ziguan District, 35% in Taoyuan District, 16% in Alian District (all in Kaohsiung City), and 23% in Baisha Township (Penghu County). Surprisingly, the Mashagou area (in Tainan City) even has a prevalence rate as high as 67% [2].

Genotype 1b is the most widespread infection of hepatitis C virus in Taiwan, accounting for 50–70% of cases. Patients with genotype 1b infection usually have a more severe disease course and are more likely to develop liver cancer. About 60.3% of HCC patients infected with the hepatitis C virus have genotype 1b, while only about 16.8% of HCC patients are infected with genotype 2a or 2c, indicating that genotype 1b is the major risk factor for liver cancer.

In addition, the distribution of hepatitis C virus genotypes differed significantly between urban and rural areas in Taiwan. In northern Taiwan, genotype 1b accounts for 58–73% of cases, and genotype 2a for 7.4–26%. Nevertheless, in southern Taiwan, genotype 1b accounts for 48–64.3%, and genotype 2a for 35.7–41.4%. Taking Kaohsiung as an example, the Kaohsiung metro area, Ziguan Township, and Taoyuan Township were mainly infected with genotype 1b, accounting for 47%, 61.9%, and 76.9%, respectively. Nevertheless, Mashagou was massively infected with genotype 2a, accounting for about 63.5% [10].

A study by Yu et al. (2015) showed that, during the period 2012–2013, nearly 45% of the patients with chronic hepatitis C in Taiwan did not receive any treatment. One of the main reasons was that patients were afraid of possible adverse side effects caused by the interferon during the treatment process (36.9%), and what is more, elderly patients over 65 years old were 2.3 times more likely to be afraid of side effects than the general patients. Other reasons include failure to meet health insurance reimbursement regulations (17.6%) and lack of awareness of treatment (11.3%). The study also showed that among those with hepatitis C, only 8.1% were willing to seek treatment from a doctor’s office and achieved successful treatment.

The Central Health Insurance Administration of the Ministry of Health and Welfare allocated NTW 3.101 billion and NTW 4.5 billion in 2016 and 2017, respectively. The funds would be used to pay for the treatment of hepatitis C and management of new oral hepatitis C drugs through optimal distribution operations to help avoid possible consumption of medical services and social resources with the development of liver cirrhosis and liver cancer in the future. With the aid of the funds, the goal of comprehensively eradicating hepatitis C is also hoped to be achieved in the near future. According to the report by the National Office for Hepatitis C Treatment, the 12-week viral load detection efficacy of the new oral drug treatment for hepatitis C was demonstrated to be remarkable, reaching a high value of 97.1% [6].

The main purpose of hepatitis C treatment is to avoid liver-related complications, and the treatment goal is to eliminate the virus so that the amount of virus in the serum can continue to be below the detection limit, i.e., to achieve the so-called “sustained viral response” (SVR, sustained virologic response). For example, SVR12 indicates the quantity of hepatitis C virus in the serum tested 12 weeks after the end of the treatment course. If no virus load is detected, the drug treatment is successful. In practice, some patients who have achieved SVR will still have their viral load detected after several years of follow-up. In those cases, most are due to re-infection rather than relapse of the original hepatitis C [11].

2.3. Rehabilitation Institutions

In Taiwan, most of the inmates in governmental correction institutions were jailed because of drug use, with an average age of 35 to 40 years old. The infection of hepatitis C is mainly through the abuse of injection drugs or the use of virus-contaminated injection needles, acupuncture needles, tattoo needles, etc. In view of the fact that most drug addicts are infected with hepatitis B, C, and HIV due to drug use, the Center for Disease Control has actively promoted the Harm Reduction Program since August 2005 to provide clean needles for drug addicts. However, since drug addicts still share needles when conducting injections, the risk of contracting blood-borne infectious diseases cannot be avoided. Therefore, for those who have been cured of drug addiction in rehabilitation institutions, free medical resources are provided.

In line with the government’s hepatitis C eradication policy, hepatitis C screening provides medically underprivileged prisoners with the opportunity to receive effective medical care. Tainan Prison Mingde Rehabilitation and Treatment Branch is the first public drug rehabilitation institution in the country. It is located in Mingde Minimum Security Prison, Shanshang District, Tainan City. It is a long and arduous road for drug-abuse inmates to rid themselves of their psychological craving and dependence on drug addiction. Because the prison is a closed environment, the inmates are unlike ordinary patients. When they feel uncomfortable, they become less willing to go to the hospital. In addition, they have seen the treatment experience of other inmates. Therefore, they are more psychologically prepared to accept those uncomfortable symptoms. After completing the course of treatment, liver C is almost healed. Consequently, if complete and continuous professional services could be provided for drug addicts in rehabilitation facilities, not only could a drug-free environment be created to help inmates develop a new healthy lifestyle, but active medical treatment may also help discover health problems for the inmates.

3. Materials and Methods

A professional staff representative took the initiative to contact the Hepatitis Prevention and Control Association first and then a public drug rehabilitation institution based in the southern district. Through a briefing to the Superintendent, a task force was organized to facilitate the project planning and monitor subsequent operation process, especially acquiring the consent of the prisoners for blood testing and follow-up consultation and treatment. The operation process is illustrated as follows.

3.1. Contact and Scheduling

Arranged a professional staff representative to contact the authority, asking about the inmate’s willingness to undergo hepatitis C screening and obtaining consent, followed by scheduling of blood screening time.

In order to make the inmates feel at ease to accept the examination, a professional team comprising a hepatologist/gastroenterologist and nurses was arranged to give lectures to the inmates. Through the lectures, the inmates could understand the impact of the disease caused by hepatitis C and explained the overall operation process. After the inmates’ concerns were relieved and consent forms collected, a blood drawing timetable was scheduled to test for hepatitis C antibodies. If the hepatitis C (Anti-HCV) antibody turned out positive, further testing of hepatitis C virus ribonucleic acid (HCV-RNA) and hepatitis C virus genotype (HCV Genotype) was conducted.

3.2. Fund-Raising and Arrangement

With funding support from the Tainan Liver Disease Prevention Foundation, free hepatitis C antibody screening and HCV RNA TYPE and viral load testing were made possible.

The average cost of screening tests is about NTW 2000 for each subject, which might be too expensive for the inmates to pay for. Therefore, the task force decided to raise funding from the Tainan City Liver Disease Prevention Foundation.

3.3. Treatment Strategy

In consideration of the inmate’s privacy and patient’s safety, a customized treatment strategy was designed and proposed for the Superintendent’s approval.

Normally, the inmates will be in handcuffs and shackles when seeking medical services outside correctional institutions. To protect the inmate’s privacy, the doctor’s consultation room was moved from the original place located on the first floor to the basement, and an abdominal ultrasound machine was set up in the consultation room. After the doctor’s consultation, the abdominal ultrasound examination could be performed in the same spot. Based on the diagnosis, a prescription was issued immediately so that each inmate could possibly return to the institution within 2 h. In addition, prescriptions would be delivered to the institution by an on-duty RN, and health education was offered if needed. Meanwhile, the institution counselor provided assistance in confirming whether the inmates took the medicine as prescribed. When the on-duty RN delivered the medicines to the institution, they would conduct blood-drawings for each inmate every week and check if any symptoms or side effects occurred.

3.4. Financial Support from Social Service Fund

In view of the fact that some inmates are in financial difficulties and unable to pay medical expenses, assistance in applying for social service funds was offered.

Basically, most inmates are economically disadvantaged. Therefore, it would be very difficult, if not impossible, for the inmates to participate in this project voluntarily. To counter this challenge, with the aid of the institutional counselor, inmates in financial need were listed and the social service fund of the hospital was used to pay for the medical expenses.

4. Results

Under the pandemic threat, two case managers were assigned to perform blood-drawing procedures in a public drug rehabilitation institution in the southern district. A total of 154 people were screened, of which 83 were positive for hepatitis C antibody screening, with a positive rate of 53.2%. There were 70 subjects with detectable viral load. It is obvious that the prevalence rate of hepatitis C in drug addicts is more than 18 times that of the general population, which is 2–3%.

For those with viral load, the age distribution shows that 21 subjects were 41–45 years old, accounting for 30%, followed by 51–55 years old (20 subjects, 28.5%), 46–50 years old (17 subjects, 30%), There were even five subjects (7.2%) who were 56–65 years old (

Table 1. Age distribution of the subjects (n = 70).

Age Category	n	%
35–40	7	10%
41–45	21	30%
46–50	17	24.3%
51–55	20	28.5%
56–65	5	7.2%
subtotal	70	100%

).

After consulting with the Superintendent, a treatment strategy was initiated, and corresponding procedures were conducted as of March 2019. The Xinhua branch hospital was appointed as the facility where treatment and service would be delivered. Among the 70 subjects with detectable viral load, 50 were retained for the treatment plan with new oral hepatitis C drugs. After a three-month follow-up, the viral load was tested again, and it turned out that no viral load reaction was detected. Moreover, 2 out of the 50 subjects did not complete the course of treatment due to personal factors; therefore, the cure rate was 97.9% (

Table 2. Viral load of the subjects (n = 50).

Viral Load IU/mL	# of Patients	%
1–1999	12	24%
2000–2999	10	20%
3000–3999	6	12%
4000–4999	2	4%
5000–5999	8	16%
6000–6999	7	14%
7000–7999	2	4%
8000–8999	1	2%
Above 9000	2	4%
subtotal	50	100%

).

Further analysis shows that among the 50 subjects who received new oral drug treatment for hepatitis C, 16 were with genotype 6a, accounting for 32%, followed by genotype 1a (9 subjects, 18%) and genotype 3a (7 subjects, 14%) (see

Table 3. Hepatitis C genotype of the subjects (n = 50).

Genotype	# of Patients	%
1a	9	18%
2a	5	10%
3a	7	14%
6a	16	32%
1b	7	14%
1a + 1b	2	4%
1a + RAS	3	6%
1a + 2	1	2%
subtotal	50	100%

). In terms of liver fibrosis, 35 patients (70%) fell into grade F0, followed by F1 (19 patients, 18%), F2 (5 patients, 10%), and F3 (1 patient, 2%) (see

Table 4. Liver fibrosis of the subjects (n = 50).

Liver Fibrosis	# of Patients	%
F0	35	70%
F1	9	18%
F2	5	10%
F3	1	2%
subtotal	50	100%

). As for the medication, most were given Epclusa (21 patients, 42%), followed by Zepatie (18 patients, 36%), Marviret (8 patients, 16%), and Zepatier + RBV (3 patients, 6%), respectively (see

Table 5. Hepatitis C medication of the subjects (n = 50).

Medication	# of Patients	%
Zepatier	18	36%
Marviret	8	16%
Epclusa	21	42%
Zepatier + RBV	3	6%
subtotal	50	100%

). In order to reduce the medical burden of individual cases, the social service fund assisted in paying a total of 24 person-times.

5. Discussion and Implications

According to a study by the Ministry of Justice, the recidivism rate of domestic drug users is as high as 80%, and in clinical experience, the success rate of life-long detoxification of heroin is only 10%. The harm caused by drugs is huge and long-term to individuals, families, and society. Most drug addicts will not seek medical advice, and, thus, experience delayed diagnosis and treatment. Significantly, many inmates entering drug rehabilitation institutions are relatively more underprivileged than the general public; therefore, they need more active medical support and assistance from medical institutions.

Through comprehensive active screening, inmates may have a better chance of receiving necessary screening tests and subsequent required medical treatment without strange vision. With a customized consultation process design, medical service providers could earn the trust of inmates in the drug rehabilitation institution and successfully complete liver C screening and treatment for the underprivileged who might otherwise delay the necessary treatment.

During this process, it was found that inmates in drug rehabilitation institutions infected with hepatitis C were mostly due to needle sharing. While the cure rate of hepatitis C is high, incidental contact with injecting drugs may easily lead to repeated infection of hepatitis C after the inmates leave the prison. It is suggested that special attention and tracking efforts must be paid to this group, supplemented with spiritual support to prevent drug addicts from going astray again.