Application of Adherence Scale and WeChat-based Continuing Nursing to Improve the Therapeutic Efficacy of Peg-IFN in CHB Patients

doi:10.21203/rs.3.rs-4520487/v1

Objective: To explore the effects of applying the eight-item Morisky Adherence Scale (MMAS-8) combined with WeChat-based continuing nursing on improving adherence and immunological response in patients with chronic hepatitis B (CHB) undergoing pegylated interferon (Peg-IFN) therapy.

Methods: A total of 156 patients diagnosed with chronic hepatitis B and initiating Peg-IFN treatment in our outpatient department from January to December 2018, who returned for follow-up after 12 weeks of treatment, were included in the study. Based on MMAS-8 evaluation results, patients were categorized into high-adherence and low-adherence groups. The high-adherence group received routine education and nursing, while the low-adherence group received WeChat-based continuing nursing. Adherence was reassessed using MMAS-8 after 48 weeks of treatment, and Peg-IFN treatment's immunological response was assessed based on laboratory indicators.

Results: Compared with baseline, at 12 weeks of treatment, the high-adherence group exhibited an immunological response rate of 44.9% (35/78), whereas the low-adherence group had a response rate of only 30.8% (24/78), showing a statistically significant difference between the groups (p<0.05, Fisher's exact test). By the 48th week of treatment with WeChat-based continuing nursing, the MMAS-8 scores were 7.0±0.6 and 7.1±0.6 in the high-adherence and low-adherence groups, respectively, with no statistically significant difference (p=0.20). There were no significant differences between the groups in immunological response rate, HBeAg seroconversion rate, or clinical cure rate.

Conclusion: In the outpatient treatment of chronic hepatitis B with Peg-IFN, the application of the adherence scale combined with WeChat-based continuing nursing not only improves patient adherence but also enhances clinical treatment outcomes.

Practice implications: Using classical scales and new media tools can help outpatient care providers deliver better care services and improve the treatment outcomes for chronic diseases.

General Practice

chronic hepatitis B

continuous nursing

adherence scale

pegylated interferon

Chronic hepatitis B (CHB) refers to infection with the hepatitis B virus (HBV) for more than 6 months, characterized by positive HBsAg and/or HBV DNA on laboratory testing. It is a major cause of cirrhosis and hepatocellular carcinoma. According to the World Health Organization, an estimated 296 million people worldwide were living with chronic HBV infection in 2019, resulting in approximately 820,000 deaths^[1]. Antiviral therapy helps delay the progression of liver fibrosis and cirrhosis, reducing the incidence of hepatocellular carcinoma and liver failure, thereby significantly improving the quality of life for patients with chronic HBV. With the advent of new antiviral drugs, particularly interferons, antiviral therapy for chronic hepatitis B has made significant progress, with most patients achieving virological response and even meeting clinical cure criteria. However, interferon therapy for chronic hepatitis B is lengthy and associated with frequent adverse effects in the initial stages, leading to low adherence rates and hindering further improvement in efficacy. Currently, outpatient nursing primarily focuses on health education and adverse reaction monitoring. This study aimed to enhance patient adherence and explore its impact on treatment outcomes by introducing an adherence scale combined with WeChat-based continuing nursing.

Study Subjects

From January to December 2018, a total of 178 patients with chronic hepatitis B who visited the Infectious Diseases Department of Changhai Hospital and initiated pegylated interferon (Peg-IFN) treatment were enrolled.

Research Proposal: Diagnosis of CHB followed the guidelines outlined in the 2019 edition of the "Guidelines for Prevention and Treatment of Chronic Hepatitis B" from the Chinese Medical Association^[2]. Education on interferon therapy for chronic hepatitis B, including treatment plans, post-injection precautions, follow-up schedules, and adverse reaction reporting and management, was provided simultaneously with the first dose of Peg-IFN. After 12 weeks of treatment, liver function, Hepatitis B Panel, and HBVquantitative testing were performed. For the Peg-IFN treatment at the 12-week follow-up, Peg-IFN treatment response was defined by meeting one of the following criteria: 1. Reduction of HBV DNA by > 2 lg IU/ml compared to baseline; 2. Decrease of HBsAg by > 1 lg IU/ml; 3. Serological conversion of HBeAg^[3]. Mean while, patient adherence was assessed using the modified Chinese version of the eight-item Morisky Medication Adherence Scale (MMAS-8), with adjustments made based on the weekly injection schedule of Peg-IFN treatment while maintaining the scoring criteria unchanged. Based on MMAS-8 scores, patients were categorized into high-adherence and low-adherence groups. Patients in the high-adherence group received standard education, while those in the low-adherence group received WeChat-based continuing nursing, including the establishment of WeChat groups, setting up reminders, and feedback mechanisms. MMAS-8 and antiviral treatment efficacy assessments were conducted again at 48 weeks of treatment. For Peg-IFN treatment at 48 weeks, preliminary clinical cure was defined as HBsAg negativity (with or without appearance of anti-HBs), undetectable HBV DNA, and normalization of liver biochemical parameters^[4]. "This study was approved by the Ethics Committee of Changhai Hospital, and all patients provided informed consent upon participation.

Statistical Analysis

Data were organized and analyzed using GraphPad Prism 8.0. Continuous variables are expressed as mean ± standard deviation, and categorical variables are presented as frequencies and percentages. Student's t-test was used for intergroup comparisons of normally distributed data, while the Mann-Whitney U test was employed for non-normally distributed data. Chi-square test or Fisher's exact test was used for group comparisons of count data. A p-value < 0.05 was considered statistically significant.

Baseline Characteristics at Initiation of Peg-IFN Therapy

A total of 178 patients with chronic hepatitis B were included, comprising 137 males and 41 females, with a mean age of 36.8 ± 9.6 years. Among them, 27 patients with HBeAg-positive liver dysfunction (ALT > upper limit of normal [ULN]), 75 with HBeAg-positive normal liver function (ALT ≤ ULN), 5 with HBeAg-negative liver dysfunction, and 71 with HBeAg-negative normal liver function.

Follow-up at 12 Weeks of Peg-IFN Therapy: After 12 weeks of Peg-IFN treatment, 156 patients underwent follow-up. Based on the modified version of the MMAS-8 scale, patients with scores ≤ 6 were categorized into the low adherence group, while those with scores > 6 were categorized into the high adherence group. The treatment response to Peg-IFN at 12 weeks is summarized in Table 1.

In the high adherence group (n = 78), there were 62 males and 16 females. In the low adherence group (n = 78), there were 61 males and 17 females. Follow-up results showed that 44.9% (35/78) of the high adherence group achieved immunologic response to Peg-IFN treatment, whereas only 30.8% (24/78) of the low adherence group achieved immunologic response. Fisher's exact test indicated a significant difference between the two groups (P < 0.05).

Twenty-two patients did not attend the follow-up visit; the main reasons for non-compliance in telephone follow-up were that these patients were from out of town (20/22) and chose to continue treatment at local hospitals. Additionally, two patients switched to other treatment plans due to severe intolerance to adverse effects and were excluded from subsequent studies.

Follow-up at 48 Weeks of Peg-IFN Therapy: With WeChat-based continuing nursing for patients in low-adherence groups, at 48 weeks of Peg-IFN therapy, the MMAS-8 scores were 7.0 ± 0.6 and 7.1 ± 0.6 in the high-adherence and low-adherence groups, respectively, with no statistically significant difference between the groups (p = 0.20). There were no significant differences between the groups in terms of immunological response rate, HBeAg seroconversion rate, or clinical cure rate(Table 2).

The main pathological mechanism underlying chronic hepatitis B is sustained viral replication and impaired antiviral immune response. Patients with chronic hepatitis B exhibit defective antiviral immune function, unable to effectively clear HBV, leading to repeated liver inflammation, hepatocyte damage, fibrosis, and progression to cirrhosis and even hepatocellular carcinoma^[5]. Current treatment strategies for chronic hepatitis B aim to suppress viral replication maximally over the long term or enhance host immune responses to improve viral clearance. Interferon, especially Peg-IFN, is recognized as an important treatment for chronic hepatitis B, achieving the dual effects of directly inhibiting viral replication and enhancing the host's immune function^{[6, 7]}. Peg-IFN therapy is characterized by a long treatment cycle, high occurrence of adverse reactions such as fever, headache, and joint pain, inconvenient administration via intramuscular injection, and impact on patient tolerance and compliance. A standardized treatment course is essential for good efficacy. Previous outpatient nursing efforts have focused on health education and collecting feedback on adverse reactions. In this study, the modified MMAS-8 scale was introduced. Different nursing strategies were adopted based on different levels of adherence. A WeChat-based continuing nursing model was implemented for patients with lower adherence to Peg-IFN therapy, with nurses fully participating in the patient's treatment process to enhance patient satisfaction and treatment efficacy.Patient treatment adherence is closely related to the effectiveness of chronic disease treatment. Poor adherence not only affects treatment outcomes but also increases the occurrence of drug resistance and adverse reactions ^[8–10]. MMAS-8 is widely used to evaluate treatment adherence among patients with chronic diseases, and its reliability and validity have been extensively verified and accepted^[10–13]. In this study, the Chinese version of the eight-item MMAS-8 scale was used, with modifications based on the administration method and treatment duration of Peg-IFN therapy for CHB. Evaluation was conducted at the 12-week follow-up visit, with patients categorized into high adherence and low adherence groups based on scores. Immunological response to Peg-IFN therapy was evaluated based on laboratory results at the 12-week follow-up and baseline results before treatment. The results showed that 44.9% (35/78) of patients in the high-adherence group achieved an immunological response, compared to only 30.8% (24/78) in the low-adherence group, with a significant difference between the two groups.

Through WeChat-based continuing nursing, dedicated nurses provided health education, treatment reminders, and collected adverse reactions, among other services, to enhance patient satisfaction and adherence. At the 48-week follow-up visit, MMAS-8 scores were again assessed, with scores of 7.0 ± 0.6 in the high-adherence group and 7.1 ± 0.6 in the low-adherence group, showing no statistical difference between the two groups. There were also no statistically significant differences between the two groups in terms of immunological response rate to Peg-IFN therapy, HBeAg seroconversion rate, or clinical cure rate, indicating that continuing nursing not only improves patient satisfaction and adherence but also enhances treatment efficacy. Overall, 47.3% (44/93) of patients who were HBeAg-positive at baseline achieved HBeAg seroconversion, and 19.9% (31/156) achieved clinical cure, similar to results from other studies^[6].

In conclusion, introducing the MMAS-8 scale during outpatient treatment for chronic hepatitis B and implementing continuing nursing to increase patient treatment adherence significantly improves patient satisfaction and treatment efficacy.

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Table 1. Immunological Response of CHB Patients After 12 Weeks of Peg-IFN Therapy

Baseline Status	High Adherence	Low Adherence
Hbe Ag + ALT>ULN	57.1%（8/14）	46.2%(6/13)
Hbe Ag + ALT≤ULN	32.1%(9/28)	23.7%(9/38)
Hbe Ag - ALT>ULN	50.0%(1/2)	33.3%(1/3)
Hbe Ag - ALT≤ULN	50.0%(17/34)	33.3%(8/24)
总计	44.9%(35/78)	30.8%(24/78)^a

a. Fisher's exact test P=0.049

Table 2. Follow-up of CHB Patients After 48 Weeks of Peg-IFN Therapy

	High Adherence	Low Adherence	P-value
MMAS-8	7.0±0.6	7.1±0.6	0.20
Immunological Response	73.1%（57/78）	71.8%（56/78）	0.50
HBe seroconversion	47.6%（20/42）	47.1%（24/51）	0.56
Clinical Cure	23.1%（18/78）	16.7%（13/78）	0.21

The authors declare no competing interests.

Application of Adherence Scale and WeChat-based Continuing Nursing to Improve the Therapeutic Efficacy of Peg-IFN in CHB Patients

Status:

Version 1

Abstract

Introduction

Methods

Results

Discussion

Conclusion

References

Tables

Additional Declarations

Status:

Version 1