Switch from intravenous or intramuscular to subcutaneous hepatitis B immunoglobulin: effect on quality of life after liver transplantation

This was a multicentre, six-month, observational study conducted at nine LT centers in Italy. The protocol was approved by the ethics committees of all participating centers. All patients provided written informed consent.

LT patients were eligible for the study if the treating physician, based on clinical judgment, decided to switch from IV or IM HBIG formulations to the SC formulation. Patients were required to be aged 18 years or older, to have undergone LT at least 1 year prior to study entry, to have received the same HBIG formulation (IV or IM) for at least the preceding 6 months, and to have sufficient cognitive capacity to understand the aims of the study and fill out the questionnaire. Patients were ineligible if they had any serious health condition that substantially reduced life expectancy, or any disease or condition that in the opinion of the investigator could interfere with completion of the study.

ITaLi-Q includes 37 items and covers eight domains (Table 1) [18]. Responses were based on a 5-point Likert scale. All crude scores were expressed as values between 0 and 100, with higher scores indicating a higher level of the dimension investigated.

The SF-36, one of the most widely used measures of health-related quality of life, consists of 36 items covering eight dimensions: physical functioning, role limitations caused by physical health problems, bodily pain, general health perception, vitality, social functioning, role limitations caused by emotional health problems, and mental health [19]. Scores on all subscales are linearly transformed to obtain a possible range of 0–100; higher scores indicate a more favorable physical functioning and psychological well-being. The eight domains may be further aggregated into two summary measures: The Physical Component Summary measure and the Mental Component Summary measure. These aggregated scores are transformed to norm-based scores (mean, 50; standard deviation, 10), with higher scores indicating more favorable physical functioning/psychological well-being [20].

Patients completed the ITaLi-Q and SF-36 questionnaires at two different time points: (i) prior to switching from IV or IM HBIG to SC HBIG and (ii) 6 months after switching. The questionnaires were handed to each patient in a sealed envelope for self-administration in an anonymous manner. Pre-specified clinical and sociodemographic data were captured for each patient and correlated with questionnaire results using a univocal numerical code.

Patient characteristics were described with means and standard deviations (SD) or medians and ranges (continuous variables) or with numbers and percentages (categorical variables). Patient characteristics were compared between the subpopulations receiving IV or IM HBIG at baseline using the Mann-Whitney U-test for continuous variables and the chi-square test or the Fisher exact test for categorical variables. Questionnaire scores at 6 months were compared to those at baseline using the Wilcoxon signed ranks test.

No formal a priori sample size estimation was performed. Instead, a sample of consecutive cases seen during a period of 12 months was identified. The actual number of patients enrolled (N = 86) provided a 99% power to detect an effect size ≥0.5 for pre-post differences across scores and a power of 79% to detect an effect size ≥0.3. An effect size of 0.5 is generally considered to be the minimum clinically relevant difference [21].

To our knowledge this is the first study to perform a detailed analysis of quality of life and treatment satisfaction of LT patients following the switch from IM HBIG or IV HBIG to SC HBIG. The two validated instruments used in the study covered both treatment-specific and general health-related quality of life domains, permitting a reliable assessment of the impact of therapy on daily life.

Results from the ITaLi-Q instrument showed that switching from IM or IV HBIG to SC HBIG was associated with a marked reduction in the perceived frequency of HBIG-related side effects, in the impact of such side effects on daily activities, and in negative feelings associated with HBIG use, such as anxiety or fatigue. The SC route of administration also reduced the impact of treatment on the flexibility of daily activities and increased patient autonomy, as documented by the striking decrease in the support required to comply with the scheduled administration of HBIG. These positive effects translated into a marked increase in treatment satisfaction, which in turn could contribute to long-term adherence with the treatment regimen. Switching to subcutaneous HBIG also exerted positive effects on broader aspects of quality of life, encompassing physical functioning, psychological well-being, and social functioning. Quality of life improvement was largely restricted to switch from SC HBIG, mostly likely because pain during intramuscular injections and the need for support for IM administration adversely affects quality of life and everyday activities. Switch from IV HBIG, administered in the hospital setting, somewhat surprisingly resulted in relatively minor improvements in quality of life. Results showed that benefits were seen only for flexibility of daily activities and the need for support to comply with the scheduled administration of HBIG, consistent with the fact that clinic visits were no longer required after introduction of SC HBIG.

From a methodological standpoint, the study shows that the ITaLi-Q instrument, in addition to its very good psychometric properties previously documented [18], is also able to capture longitudinal changes in the impact of the HBIG therapy on daily activities and patient satisfaction.

Few studies have investigated the impact of different HBIG modalities on quality of life and satisfaction in LT patients. Previously, we reported that patients treated with IM HBIG had significantly higher scores for the ITaLi-Q flexibility and the negative feelings domains than patients given IV HBIG, but lower scores for the side effects domain [18]. A small study in 12 patients conducted at the Vancouver General Hospital investigated the effect of conversion from IM HBIG to SC HBIG. On a pain rating scale of 0 to 10, patients rated their previous IM injections as 5, whereas SC administration was rated as 1.6 [22, 23]. Moreover, all patients reported a preference for SC administration versus IM administration. More recently, a prospective, observational study assessed compliance and tolerability in maintenance LT patients self-administering SCs HBIG at home according to local practice [24]. Patient compliance was graded good or very good by physicians in 91.8% of cases, and treatment was well-tolerated, with no interruption or discontinuation of treatment due to adverse events.

To our knowledge, no data exist on the impact on quality of life of converting from IV HBIG to SC HBIG.

Study results could have important implications for clinical practice. Increasing the acceptability of HBIG therapy can help to increase treatment compliance and reduce the risk of post-transplant HBV reinfection. The current findings indicate that the SC route of administration markedly improves the acceptability of treatment, by reducing side effects and their interference with daily life, ameliorating negative feelings, and increasing patient autonomy. Reducing the need for in-hospital administration of HBIG by switching to SC therapy would also be expected to lower health care costs. The striking improvement in treatment satisfaction further suggests that SC HBIG can represent the treatment of choice for most LT patients.

The study has limitations. First, patients who were proposed to switch from the previous modality of HBIG administration to the subcutaneous modality could be those reporting higher perceived HBIG-related side effects. Second, we have no information on those patients who were proposed the new route of administration, but refused to use it. Therefore, our study population could be not fully representative of patients treated with HBIG. Despite these limitations, our study shows that many patients can derive a substantial benefit from switching to SC therapy.