Multi-disciplinary cooperation for the micro-elimination of hepatitis C in China: a hospital-based experience

In August 2021, a hepatitis C multi-disciplinary cooperation group was formed at the hospital, led by the hospital leader. This group integrated various medical resources from departments such as medical affairs, prevention and healthcare, hospital-acquired infection control, infectious diseases, gastroenterology, clinical laboratory, information management, and pharmacy.

The medical affairs department formulated and improved testing strategies, including implementing hepatitis C examination regulations for patients undergoing surgery, hospitalisation, haemodialysis, invasive diagnosis, and treatment. The hospital-acquired infection control department focused on preventing iatrogenic infections. The clinical laboratory department implemented a system to remind clinicians to order HCV RNA tests for patients with positive anti-HCV test results and added notes on reports with positive HCV RNA results to visit the hepatitis C clinic in the gastroenterology department. The information management office upgraded the infectious disease reporting and management system, enabling automatic Short Message Service (SMS) notifications to doctors in charge of patients with positive anti-HCV or HCV RNA results regarding follow-up diagnosis and treatment. Public health doctors in the prevention and healthcare department focused on quality control, while monitoring and managing patients with hepatitis C through an infectious disease information reporting platform, providing follow-up, treatment recommendations, and educating patients and their close contacts via health education prescriptions and offline lectures. The departments collaborated closely to improve and standardise hepatitis C screening, diagnosis, referral, and follow-up processes. The specific division of responsibilities of the cooperation group is shown in Fig. 1. A brief description of the management of patients who were positive for hepatitis C antibodies is shown in Fig. 2.

Data were presented as frequencies and percentages (%). The rates were compared between the groups using the Chi-square test. The trends of the rates were tested using a Chi-square test for a linear trend. The Pearson correlation coefficient (r) was used to assess whether the correlation was positive or negative. A multivariable logistic regression was conducted to analyse factors influencing antiviral therapy in RNA-positive patients. All the tests were two-tailed, and statistical significance was set at P < 0.05. All analyses were performed using IBM Statistical Product and Service Solutions (SPSS), version 25. Rates were calculated as follows:

Overall, 393,459 patients were screened between 2016 and 2022. Among them, 205,122 (52.133%) were male. The anti-HCV antibody-positivity rate was 0.332% (95% confidence interval [CI], 0.314%–0.350%), with 1,306 patients testing positive. Male patients had a higher HCV-positivity rate than female patients (0.372% vs. 0.287%, χ² = 21.282, P < 0.001). The median age of anti-HCV antibody-positive patients was 54 years. Furthermore, the 25th and 75th percentiles were 39 and 65 years, respectively. The maximum age was 100 years, and the minimum age was 1 day.

According to the age group, the positivity rate of anti-HCV antibodies was 0.148% among people aged 0–19 years, which was the lowest rate, while the highest rate was observed in the 40–59-year group (0.389%). Overall, 84.533% (1104/1306) of the patients positive for anti-HCV antibodies were over 40 years. The HCV antibody-positivity rate showed an increasing trend with ages (χ²_line = 45.332, r = 0.011, P < 0.001) (Fig. 3). Additionally, there was a significant increase in the anti-HCV-positivity rate, yearly from 2016 to 2022 (χ²_line = 20.417, r = 0.007, P = 0.002) (Fig. 4).

This retrospective analysis of hepatitis C serology revealed that among 1,306 anti-HCV-positive cases, more men than women tested positive, potentially attributable to the higher trends of unsafe exposure behaviour in men [21]. Similar findings were reported in other studies [10, 19]. Furthermore, 84.533% of the patients were aged ≥ 40 years, highlighting the need for increased anti-HCV screening in male patients ≥ 40 years [22, 23]. Our findings also showed an annual increase in the anti-HCV antibody-positivity rate, consistent with the observations from previous research [24, 25]. However, hepatitis C elimination has been delayed owing to the impact of COVID-19, and national HCV surveillance systems are still being established. Only 18% of patients with hepatitis C in China had been diagnosed correctly. Although 25% of patients were in need of urgent treatment, only 1.3% had access to treatment [26].

Before the multi-disciplinary cooperation, doctors at this hospital had limited awareness of hepatitis C, and only 51.899% of the clinicians recognised DAAs as the preferred treatment, while approximately 32.911% believed that asymptomatic patients did not require treatment. The professional experience and perception regarding hepatitis C among physicians can affect the medical behaviour and willingness of patients to receive treatment significantly [27, 28]. In this study, we found that before the implementation, 36.426% of the anti-HCV-positive patients had undergone confirmatory HCV RNA testing, 67.456% of the RNA-positive patients were diagnosed correctly with hepatitis C, and only 12.426% of the RNA-positive patients received antiviral therapy. Overall, referral diagnosis and treatment rates were low, as observed in other countries [29].

Under the multi-disciplinary cooperation, public health doctors supervised the process, by using the infectious disease reporting and management platform to track RNA detection in patients with anti-HCV positivity, communicate with the doctor in charge, and ensure timely HCV RNA testing. Active follow-ups are recommended through SMS or phone calls, to spread awareness about treatment and prevention and ensure that new patients with hepatitis C in the hospital complete their treatment course. This study showed that 88.737% of patients with anti-HCV positivity were prescribed an HCV RNA test, 98.113% of the RNA-positive patients were diagnosed with hepatitis C, and 58.491% were referred for treatment.

However, the treatment rate still fell short of the target of 80% of hepatitis C patients receiving treatment. In this regard, multivariable logistic regression analysis revealed adverse factors for HCV antiviral therapy, including age ≥ 40 years, non-local residency; urban resident insurance; lack of intervention by medical institutions; and absence of liver fibrosis or tumours or other serious diseases (including oesophageal cancer, gastric cancer, haemophilia, and syringomyelia). Among these factors, the OR for multi-disciplinary cooperation in medical institutions showed the strongest correlation and it was the most important factor for patients to undergo HCV treatment. Implementing multi-disciplinary cooperation in all healthcare settings can facilitate the elimination of hepatitis C.

To eliminate hepatitis C by 2030, China must treat at least 550,000 cases annually [30]. Since 2017, an increasing number of DAAs have been approved [31]. Currently, eight DAAs are included in the national medical insurance directory, which has greatly reduced the economic burden on patients with hepatitis C. For example, regarding sofosbuvir/velpatasvir (SOF/VEL), a pan-genotypic drug, before including the drug in the national medical insurance drug negotiations, the cost of a full treatment course was approximately $12,000. Currently, the drug cost is approximately $1500. After including SOF/VEL in the medical insurance negotiations, the maximum cost of the full treatment course was not more than $900 under the urban resident basic medical insurance, while it was $600 under the employee health insurance, which improved drug accessibility. Our study showed that employee health insurance was a favourable factor for antiviral therapy in patients with HCV because it requires a lower percentage of out-of-pocket expenses.

In September 2021, the National Health Commission of China, the Ministry of Science and Technology, and nine other departments formulated and issued the Work Plan for Action to Eliminate the Public Health Hazards of Hepatitis C (2021–2030) [32]. Thus, the government aims to implement effective measures to significantly prevent and control hepatitis C, curb new infections, effectively detect and cure patients, and reduce mortality from liver cirrhosis and cancer caused by hepatitis C. The Work Plan also proposed specific action targets for 2021, 2025, and 2030.

Although we improved the hepatitis C diagnosis rate, the treatment rate remains suboptimal. First, DAAs are not always available at many medical institutions. A study by the Chinese Centre for Disease Control and Prevention found that only 10.84% of medical institutions followed the standard treatment guidelines for hepatitis C in 2020 [33]. Our study showed lower treatment rates for patients from other cities, possibly because of the limited access to treatment in their city. The lack of DAAs drugs in hospital facilities is an important factor. Under the diagnosis-related group/diagnosis-intervention packet payment reform, the health insurance fund will make settlements according to the established payment standard. The medical institutions will bear the excess medical expenses over the base payment. If there is a surplus, it can be used as income for the hospital [34]. Therefore, the high cost of the negotiated drugs poses cost control challenges, further reducing motivation to introduce DAAs. On April 22, 2021, the National Healthcare Administration and the National Health Commission jointly issued the Guidance on Establishing and Improving the Dual-Channel Management Mechanism for negotiated drugs under the national medical insurance jointly [35]. Consequently, after clinicians at the hospital issue the prescriptions, patients can purchase and pay for the relevant drugs in the designated pharmacy covered by the medical insurance, without a proportional increase in drug costs contributing to the total health expenditure. However, to date, the policy has not been well implemented, and most hospitals still do not operate a dual-channel mechanism.

Second, only 46.1% of the medical institutions in China are able to conduct RNA testing [33]. Furthermore, hospitals capable of RNA testing accumulate samples for cost efficiency, impacting the accuracy of the RNA results. Simultaneously, if the RNA test results are released after the patients are discharged, treatment initiation will not be conducive, particularly for non-local patients, which can affect the treatment rate.

Third, China only began to include DAAs in the Category B list of medical insurance in 2019, and the treatment is not yet universal. Currently, clinicians may not fully understand the clinical indications for hepatitis C antiviral drugs, especially the impact of DAAs on patients with hepatitis C combined with tumours or other serious diseases. The follow-up results of the patients who tested positive for HCV RNA revealed that the treatment rate was low for those aged ≥ 60 years or with tumours or other serious diseases. However, some patients and doctors may decline the hepatitis C treatment due to a lack of awareness regarding the types of medication and importance of treating hepatitis C.

This study had several limitations. First, this was a retrospective study that was conducted in a single centre that included experience sharing, despite our institution being a large, regional, comprehensive grade-A hospital that treats patients with various diseases. However, the findings may reflect the real-world situation of hepatitis C in the region. Future studies could use multiple, decentralised diagnostic care pathways to improve the detection of potential infections [36]. This may help us better understand the local prevalence of hepatitis C. Second, treatment information was primarily obtained from medical records and via telephone follow-up interviews. Currently, a transformation of the treatment and follow-up data platform has been initiated at our hospital. In the future, clinicians will be able to directly input relevant information to improve the accuracy of treatment-related data. Finally, there was still a percentage of anti-HCV( +) patients who did not receive HCV RNA tests. The gap in accurate HCV RNA diagnosis requires reduction; however, due to the layout of the hospital districts, we could not perform a reflex testing model, such as that built by Huang et al. [37]. Future studies should be performed in centres which allow for rapid blood sample transfer from collection to testing for such analysis.