Treatment adherence – Room for improvement, not only in autoimmune hepatitis
Authors: Christina Weiler-Normann, Ansgar W. Lohse
Journal: Journal of Hepatology (2012)

Identifying opportunities to improve management of autoimmune hepatitis: Evaluation of drug adherence and psychosocial factorsJournal of HepatologyVol. 57Issue 6PreviewRecognizing the importance of adherence to therapy in autoimmune hepatitis (AIH) is critical for patient care and avoidance of unnecessary intervention. The influence of psychosocial factors on treatment adherence needs better understanding and prominence. We sought to determine the association between anxiety, depressive symptoms, and avoidant relationship style on self-reported immunosuppressant medication adherence and treatment response in patients with AIH. Full-Text PDF Prescribing medication and explaining how to take it, what side effects and benefits it may have, are core activities of every physician and hepatologist. It has been shown that straightforward review of the patients’ medication intake is not conducted routinely [[1]Tarn D.M. Paterniti D.A. Kravitz R.L. Fein S. Wenger N.S. How do physicians conduct medication reviews?.J Gen Intern Med. 2009; 24: 1296-1302Crossref PubMed Scopus (26) Google Scholar]. Physicians rarely ask their patients about their adherence to the prescribed medication [[2]Barfod T.S. Hecht F.M. Rubow C. Gerstoft J. Physicians’ communication with patients about adherence to HIV medication in San Francisco and Copenhagen: a qualitative study using Grounded Theory.BMC Health Serv Res. 2006; 6: 154Crossref PubMed Scopus (37) Google Scholar]. At the same time, the increasing use of potent anti-infective therapy has clearly demonstrated the importance of patient adherence. Nowadays, clinical studies have proposed different means of measuring adherence as objectively as possible. However, it appears that adherence rates assessed with these measures are unsatisfactory [3Marengo M. Waimann C. Achaval S. Zhang H. Garcia-Gonzalez A. Richardson M. et al.Measuring therapeutic adherence in systemic lupus erythematosus with electronic monitoring.Lupus. 2012; 21: 1158-1165Crossref PubMed Scopus (58) Google Scholar, 4Shi L. Liu J. Koleva Y. Fonseca V. Kalsekar A. Pawaskar M. Concordance of adherence measurement using self-reported adherence questionnaires and medication monitoring devices.Pharmacoeconomics. 2010; 28: 1097-1107Crossref PubMed Scopus (153) Google Scholar]. Objectively measured adherence may differ quite substantially from self-reported medication adherence [[5]Wiens M.O. Macleod S. Musiime V. Ssenyonga M. Kizza R. Bakeera-Kitaka S. et al.Adherence to antiretroviral therapy in HIV-positive adolescents in Uganda assessed by multiple methods: a prospective cohort study.Paediatr Drugs. 2012; 14: 331-335Crossref PubMed Google Scholar].Many different factors may influence adherence to drug regimens [6Brown M.T. Bussell J.K. Medication adherence: WHO cares?.Mayo Clin Proc. 2011; 86: 304-314Abstract Full Text Full Text PDF PubMed Scopus (1099) Google Scholar, 7Osterberg L. Blaschke T. Adherence to medication.N Engl J Med. 2005; 353: 487-497Crossref PubMed Scopus (6024) Google Scholar] (summarized in Table 1): on the one hand, factors attributable to the patients such as psychiatric disorders, psychological distress, presence of depression or anxiety, lower formal education or communication barriers, marital status, older or younger age, poverty, geographic clustering [[8]Hoang C. Kolenic G. Kline-Rogers E. Eagle K.A. Erickson S.R. Mapping geographic areas of high and low drug adherence in patients prescribed continuing treatment for acute coronary syndrome after discharge.Pharmacotherapy. 2011; 31: 927-933Crossref PubMed Scopus (15) Google Scholar] and many more have been shown to have a negative impact on drug-adherence. On the other hand, a favorable view about the goals of treatment and informed consent improve drug-adherence. In addition, there are factors having an impact on adherence attributable to the treating physician: prescription of complex therapeutic regimens containing many different pills and/or time points [[7]Osterberg L. Blaschke T. Adherence to medication.N Engl J Med. 2005; 353: 487-497Crossref PubMed Scopus (6024) Google Scholar], ineffective communication about effects and possible side effects of the medication as well as incomplete information about the disease itself and the therapeutic regimen may all negatively affect adherence. Detailed education of patients has been shown to be particularly important as patients may have very different ideas of the disease’s pathogenesis and possible influencing factors [[9]Marshall I.J. Wolfe C.D. McKevitt C. Lay perspectives on hypertension and drug adherence: systematic review of qualitative research.BMJ. 2012; 345: e3953Crossref PubMed Scopus (221) Google Scholar]. These discrepancies of information level between laymen’s views and physicians’ views have a direct negative effect on adherence.Table 1Factors influencing drug adherence. Open table in a new tab In addition to factors attributable to the patient or the physician, there are disease-related factors that are specifically relevant in the setting of chronic diseases. Although these factors may be difficult to differentiate from patient-related factors, they deserve additional attention as their consideration may facilitate and improve treatment success.In chronic liver diseases such as autoimmune hepatitis (AIH), drug adherence can be particularly difficult, and is at the same time particularly important. Untreated AIH has a poor prognosis, while adequate treatment results in excellent prognosis [10Yoshizawa K. Matsumoto A. Ichijo T. Umemura T. Joshita S. Komatsu M. et al.Long-term outcome of Japanese patients with type 1 autoimmune hepatitis.Hepatology. 2012; 56: 668-676Crossref PubMed Scopus (87) Google Scholar, 11Kanzler S. Lohr H. Gerken G. Galle P.R. Lohse A.W. Long-term management and prognosis of autoimmune hepatitis (AIH): a single center experience.Z Gastroenterol. 2001; 39 (344–348): 339-341Crossref PubMed Scopus (109) Google Scholar]. Patients may be alienated by the unknown pathogenesis with an often asymptomatic or oligosymptomatic course and the need of potent immunosuppressive treatment. Sudden flares without trigger may occur and unsettle the patient further. Reading the instruction leaflets of the most frequently prescribed medications prednisone, azathioprine or mycophenolate mofetil is unlikely to encourage the patient’s motivation for drug adherence. The long list of potential side effects as well as the subjectively perceived and objectively possible consequences of initially high steroid doses may frighten patients.The study by Sockalingam and colleagues [[12]Sockalingam S. Blank D. Abdelhamid N. Abbey S.E. Hirschfield G.M. Identifying opportunities to improve management of autoimmune hepatitis: evaluation of drug adherence and psychosocial factors.J Hepatol. 2012; 57: 1299-1304Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar] in this issue focuses on patient-related factors by analyzing a cohort of 57 well-defined patients suffering from AIH: these patients treated for AIH at a tertiary care center were asked to report their adherence on a visual scale from 1 to 100. In addition they were asked to complete different validated questionnaires regarding their anxiety level (GAD7, Generalized Anxiety Disorder-7), presence of depression (PHQ9, Patient Health Questionnaire-9) and relationship style (ECR-16; Experiences in Close Relationship Scale). Treatment response to standard immunosuppressive treatment was determined by liver biochemistry and immunoglobulin G levels. Not surprisingly, treatment response was associated with higher self-reported adherence underlining that the conventional treatment with azathioprine or mycophenolate mofetil in addition to prednisone is effective when actually taken.In general, adherence was rather high in this group of patients with more than 80 percent of the patients reporting drug-adherence of more than 80%. This finding compares favorably to other diseases in a non-transplant setting [[3]Marengo M. Waimann C. Achaval S. Zhang H. Garcia-Gonzalez A. Richardson M. et al.Measuring therapeutic adherence in systemic lupus erythematosus with electronic monitoring.Lupus. 2012; 21: 1158-1165Crossref PubMed Scopus (58) Google Scholar], especially when taking into account that many of these patients were probably asymptomatic. The results, however, may be biased by the fact that patients attending a tertiary care center are likely to be more motivated than the average patient seeing a general practitioner. In addition, there is a positive selection bias as study participation was voluntary, thus probably including primarily more cooperative and motivated patients.Evidently, non-responders had more anxiety symptoms and higher ECR avoidance scores. Anxiety is often associated with misconceptions of the pathogenesis and course of diseases and may increase with poor treatment response, but may also be a predisposing factor for non-adherence. Isolating causality is of course challenging and problematic. The current study was designed to analyze adherence rather than to answer this more philosophical question, but the fact that ECR avoidance scores are one expression of a relationship style and an almost stable personality trait not easily influenced by external factors, suggests that anxiety was present in patients prior to the diagnosed AIH. Among the treatment non-responders in this study, 25% reported adherence of less than 80% on a visual analogue scale. These patients showed higher scores on the GAD7, PHQ9 and ECR-avoidance score in addition to having worse laboratory outcomes compared to the patients reporting adherence of ⩾80%. It is important to point out that the current study did not question patients about their reasons for non-adherence, which would yield important information for planning future interventional studies. Do patients simply forget to take their pills, as is being reported to be a major reason in many other adherence studies, or are there other reasons such as concerns about side effects, feeling less control over their lives and poor life satisfaction? [13Chisholm-Burns M, Pinsky B, Parker G, Johnson P, Arcona S, Buzinec P, et al. Factors related to immunosuppressant medication adherence in renal transplant recipients. Clin Transplant 2012 [Epub ahead of print].Google Scholar, 14Wakibi S.N. Ng’ang’a Z.W. Mbugua G.G. Factors associated with non-adherence to highly active antiretroviral therapy in Nairobi, Kenya.AIDS Res Ther. 2012; 8: 43Crossref Scopus (31) Google Scholar].Drug-adherence is rarely discussed with patients, and physicians may not be sufficiently aware of this problem. Poor drug-adherence may endanger patients for two reasons: firstly, they have an inefficient first-line treatment that may jeopardize recovery and put them at risk for progression of AIH. Secondly, poor treatment response is mostly misinterpreted as non-response rather than non-adherence and therefore typically triggers adaptation of immunosuppressive treatment. Higher steroid doses, as nicely shown in this study, may be associated with higher rates of depression. Administration of more potent and potentially hazardous agents such as calcineurin inhibitors or cyclophosphamide may cause an increase in anxiety in addition to causing possible new side effects. These measures are therefore counterproductive in a patient who may have been non-adherent to first-line treatments.Solving this dilemma is certainly not easy and will require talking to patients about drug adherence as well as trying to identify and address factors that may negatively influence drug-adherence. Gently assessing adherence in a way that will not embarrass the patient or lead them to deny their non-adherence can help identify patients at risk. Careful education of patients has been shown to positively impact anxiety levels e.g., in preoperative settings [[15]Sjoling M. Nordahl G. Olofsson N. Asplund K. The impact of preoperative information on state anxiety, postoperative pain and satisfaction with pain management.Patient Educ Couns. 2003; 51: 169-176Abstract Full Text Full Text PDF PubMed Scopus (211) Google Scholar] and, at the same time shows substantial effect on drug adherence [[16]Pepper J.K. Carpenter D.M. DeVellis R.F. Does adherence-related support from physicians and partners predict medication adherence for vasculitis patients?.J Behav Med. 2012; 35: 115-123Crossref PubMed Scopus (13) Google Scholar]. Ideally, objective measures of drug adherence should be put in place, but it is certainly unrealistic to refer to clinic-based pill counts, electronic systems or other technical means of control. Measurements of 6-thioguanine-nucleotide levels that reflect azathioprine adherence to a certain extent are possible, but certainly do not replace a trustful relationship between a chronically ill patient and their physician. Implementation of follow-up actions, incentives or perhaps eTools to help patients [17Haynes RB, Ackloo E, Sahota N, McDonald HP, Yao X. Interventions for enhancing medication adherence. Cochrane Database Syst Rev 2008; CD000011.Google Scholar, 18Mahtani KR, Heneghan CJ, Glasziou PP, Perera R. Reminder packaging for improving adherence to self-administered long-term medications. Cochrane Database Syst Rev 2011; CD005025.Google Scholar] will improve patients’ adherence and also their disease progression. The importance of drug adherence should be openly addressed and combined with education and information on the disease and the rationale of treatment. Having identified this critical problem in the care of patients suffering from AIH, the study demonstrates that additional research is necessary to investigate the physician-related and disease-related factors having an impact on drug-adherence. Furthermore, studies examining interventions in order to improve adherence are necessary.Chronic diseases ask for patient autonomy and shared decision-making. Examining adherence openly in a non-accusing manner should be a routine part of every visit as well as identification of factors that may predispose for poor adherence – not only in patients suffering from AIH. Tackling these factors may be difficult and time-consuming but worthwhile, as there are multiple studies suggesting increases in drug adherence lead to possible reduction of total health care cost [19Roebuck M.C. Liberman J.N. Gemmill-Toyama M. Brennan T.A. Medication adherence leads to lower health care use and costs despite increased drug spending.Health Aff (Millwood). 2011; 30: 91-99Crossref PubMed Scopus (337) Google Scholar, 20Desborough J.A. Sach T. Bhattacharya D. Holland R.C. Wright D.J. A cost-consequences analysis of an adherence focused pharmacist-led medication review service.Int J Pharm Pract. 2012; 20: 41-49Crossref PubMed Scopus (24) Google Scholar] and hopefully also better patient-physician relationships as well as healthier patients.Conflict of interestThe authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript. Prescribing medication and explaining how to take it, what side effects and benefits it may have, are core activities of every physician and hepatologist. It has been shown that straightforward review of the patients’ medication intake is not conducted routinely [[1]Tarn D.M. Paterniti D.A. Kravitz R.L. Fein S. Wenger N.S. How do physicians conduct medication reviews?.J Gen Intern Med. 2009; 24: 1296-1302Crossref PubMed Scopus (26) Google Scholar]. Physicians rarely ask their patients about their adherence to the prescribed medication [[2]Barfod T.S. Hecht F.M. Rubow C. Gerstoft J. Physicians’ communication with patients about adherence to HIV medication in San Francisco and Copenhagen: a qualitative study using Grounded Theory.BMC Health Serv Res. 2006; 6: 154Crossref PubMed Scopus (37) Google Scholar]. At the same time, the increasing use of potent anti-infective therapy has clearly demonstrated the importance of patient adherence. Nowadays, clinical studies have proposed different means of measuring adherence as objectively as possible. However, it appears that adherence rates assessed with these measures are unsatisfactory [3Marengo M. Waimann C. Achaval S. Zhang H. Garcia-Gonzalez A. Richardson M. et al.Measuring therapeutic adherence in systemic lupus erythematosus with electronic monitoring.Lupus. 2012; 21: 1158-1165Crossref PubMed Scopus (58) Google Scholar, 4Shi L. Liu J. Koleva Y. Fonseca V. Kalsekar A. Pawaskar M. Concordance of adherence measurement using self-reported adherence questionnaires and medication monitoring devices.Pharmacoeconomics. 2010; 28: 1097-1107Crossref PubMed Scopus (153) Google Scholar]. Objectively measured adherence may differ quite substantially from self-reported medication adherence [[5]Wiens M.O. Macleod S. Musiime V. Ssenyonga M. Kizza R. Bakeera-Kitaka S. et al.Adherence to antiretroviral therapy in HIV-positive adolescents in Uganda assessed by multiple methods: a prospective cohort study.Paediatr Drugs. 2012; 14: 331-335Crossref PubMed Google Scholar]. Many different factors may influence adherence to drug regimens [6Brown M.T. Bussell J.K. Medication adherence: WHO cares?.Mayo Clin Proc. 2011; 86: 304-314Abstract Full Text Full Text PDF PubMed Scopus (1099) Google Scholar, 7Osterberg L. Blaschke T. Adherence to medication.N Engl J Med. 2005; 353: 487-497Crossref PubMed Scopus (6024) Google Scholar] (summarized in Table 1): on the one hand, factors attributable to the patients such as psychiatric disorders, psychological distress, presence of depression or anxiety, lower formal education or communication barriers, marital status, older or younger age, poverty, geographic clustering [[8]Hoang C. Kolenic G. Kline-Rogers E. Eagle K.A. Erickson S.R. Mapping geographic areas of high and low drug adherence in patients prescribed continuing treatment for acute coronary syndrome after discharge.Pharmacotherapy. 2011; 31: 927-933Crossref PubMed Scopus (15) Google Scholar] and many more have been shown to have a negative impact on drug-adherence. On the other hand, a favorable view about the goals of treatment and informed consent improve drug-adherence. In addition, there are factors having an impact on adherence attributable to the treating physician: prescription of complex therapeutic regimens containing many different pills and/or time points [[7]Osterberg L. Blaschke T. Adherence to medication.N Engl J Med. 2005; 353: 487-497Crossref PubMed Scopus (6024) Google Scholar], ineffective communication about effects and possible side effects of the medication as well as incomplete information about the disease itself and the therapeutic regimen may all negatively affect adherence. Detailed education of patients has been shown to be particularly important as patients may have very different ideas of the disease’s pathogenesis and possible influencing factors [[9]Marshall I.J. Wolfe C.D. McKevitt C. Lay perspectives on hypertension and drug adherence: systematic review of qualitative research.BMJ. 2012; 345: e3953Crossref PubMed Scopus (221) Google Scholar]. These discrepancies of information level between laymen’s views and physicians’ views have a direct negative effect on adherence. In addition to factors attributable to the patient or the physician, there are disease-related factors that are specifically relevant in the setting of chronic diseases. Although these factors may be difficult to differentiate from patient-related factors, they deserve additional attention as their consideration may facilitate and improve treatment success. In chronic liver diseases such as autoimmune hepatitis (AIH), drug adherence can be particularly difficult, and is at the same time particularly important. Untreated AIH has a poor prognosis, while adequate treatment results in excellent prognosis [10Yoshizawa K. Matsumoto A. Ichijo T. Umemura T. Joshita S. Komatsu M. et al.Long-term outcome of Japanese patients with type 1 autoimmune hepatitis.Hepatology. 2012; 56: 668-676Crossref PubMed Scopus (87) Google Scholar, 11Kanzler S. Lohr H. Gerken G. Galle P.R. Lohse A.W. Long-term management and prognosis of autoimmune hepatitis (AIH): a single center experience.Z Gastroenterol. 2001; 39 (344–348): 339-341Crossref PubMed Scopus (109) Google Scholar]. Patients may be alienated by the unknown pathogenesis with an often asymptomatic or oligosymptomatic course and the need of potent immunosuppressive treatment. Sudden flares without trigger may occur and unsettle the patient further. Reading the instruction leaflets of the most frequently prescribed medications prednisone, azathioprine or mycophenolate mofetil is unlikely to encourage the patient’s motivation for drug adherence. The long list of potential side effects as well as the subjectively perceived and objectively possible consequences of initially high steroid doses may frighten patients. The study by Sockalingam and colleagues [[12]Sockalingam S. Blank D. Abdelhamid N. Abbey S.E. Hirschfield G.M. Identifying opportunities to improve management of autoimmune hepatitis: evaluation of drug adherence and psychosocial factors.J Hepatol. 2012; 57: 1299-1304Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar] in this issue focuses on patient-related factors by analyzing a cohort of 57 well-defined patients suffering from AIH: these patients treated for AIH at a tertiary care center were asked to report their adherence on a visual scale from 1 to 100. In addition they were asked to complete different validated questionnaires regarding their anxiety level (GAD7, Generalized Anxiety Disorder-7), presence of depression (PHQ9, Patient Health Questionnaire-9) and relationship style (ECR-16; Experiences in Close Relationship Scale). Treatment response to standard immunosuppressive treatment was determined by liver biochemistry and immunoglobulin G levels. Not surprisingly, treatment response was associated with higher self-reported adherence underlining that the conventional treatment with azathioprine or mycophenolate mofetil in addition to prednisone is effective when actually taken. In general, adherence was rather high in this group of patients with more than 80 percent of the patients reporting drug-adherence of more than 80%. This finding compares favorably to other diseases in a non-transplant setting [[3]Marengo M. Waimann C. Achaval S. Zhang H. Garcia-Gonzalez A. Richardson M. et al.Measuring therapeutic adherence in systemic lupus erythematosus with electronic monitoring.Lupus. 2012; 21: 1158-1165Crossref PubMed Scopus (58) Google Scholar], especially when taking into account that many of these patients were probably asymptomatic. The results, however, may be biased by the fact that patients attending a tertiary care center are likely to be more motivated than the average patient seeing a general practitioner. In addition, there is a positive selection bias as study participation was voluntary, thus probably including primarily more cooperative and motivated patients. Evidently, non-responders had more anxiety symptoms and higher ECR avoidance scores. Anxiety is often associated with misconceptions of the pathogenesis and course of diseases and may increase with poor treatment response, but may also be a predisposing factor for non-adherence. Isolating causality is of course challenging and problematic. The current study was designed to analyze adherence rather than to answer this more philosophical question, but the fact that ECR avoidance scores are one expression of a relationship style and an almost stable personality trait not easily influenced by external factors, suggests that anxiety was present in patients prior to the diagnosed AIH. Among the treatment non-responders in this study, 25% reported adherence of less than 80% on a visual analogue scale. These patients showed higher scores on the GAD7, PHQ9 and ECR-avoidance score in addition to having worse laboratory outcomes compared to the patients reporting adherence of ⩾80%. It is important to point out that the current study did not question patients about their reasons for non-adherence, which would yield important information for planning future interventional studies. Do patients simply forget to take their pills, as is being reported to be a major reason in many other adherence studies, or are there other reasons such as concerns about side effects, feeling less control over their lives and poor life satisfaction? [13Chisholm-Burns M, Pinsky B, Parker G, Johnson P, Arcona S, Buzinec P, et al. Factors related to immunosuppressant medication adherence in renal transplant recipients. Clin Transplant 2012 [Epub ahead of print].Google Scholar, 14Wakibi S.N. Ng’ang’a Z.W. Mbugua G.G. Factors associated with non-adherence to highly active antiretroviral therapy in Nairobi, Kenya.AIDS Res Ther. 2012; 8: 43Crossref Scopus (31) Google Scholar]. Drug-adherence is rarely discussed with patients, and physicians may not be sufficiently aware of this problem. Poor drug-adherence may endanger patients for two reasons: firstly, they have an inefficient first-line treatment that may jeopardize recovery and put them at risk for progression of AIH. Secondly, poor treatment response is mostly misinterpreted as non-response rather than non-adherence and therefore typically triggers adaptation of immunosuppressive treatment. Higher steroid doses, as nicely shown in this study, may be associated with higher rates of depression. Administration of more potent and potentially hazardous agents such as calcineurin inhibitors or cyclophosphamide may cause an increase in anxiety in addition to causing possible new side effects. These measures are therefore counterproductive in a patient who may have been non-adherent to first-line treatments. Solving this dilemma is certainly not easy and will require talking to patients about drug adherence as well as trying to identify and address factors that may negatively influence drug-adherence. Gently assessing adherence in a way that will not embarrass the patient or lead them to deny their non-adherence can help identify patients at risk. Careful education of patients has been shown to positively impact anxiety levels e.g., in preoperative settings [[15]Sjoling M. Nordahl G. Olofsson N. Asplund K. The impact of preoperative information on state anxiety, postoperative pain and satisfaction with pain management.Patient Educ Couns. 2003; 51: 169-176Abstract Full Text Full Text PDF PubMed Scopus (211) Google Scholar] and, at the same time shows substantial effect on drug adherence [[16]Pepper J.K. Carpenter D.M. DeVellis R.F. Does adherence-related support from physicians and partners predict medication adherence for vasculitis patients?.J Behav Med. 2012; 35: 115-123Crossref PubMed Scopus (13) Google Scholar]. Ideally, objective measures of drug adherence should be put in place, but it is certainly unrealistic to refer to clinic-based pill counts, electronic systems or other technical means of control. Measurements of 6-thioguanine-nucleotide levels that reflect azathioprine adherence to a certain extent are possible, but certainly do not replace a trustful relationship between a chronically ill patient and their physician. Implementation of follow-up actions, incentives or perhaps eTools to help patients [17Haynes RB, Ackloo E, Sahota N, McDonald HP, Yao X. Interventions for enhancing medication adherence. Cochrane Database Syst Rev 2008; CD000011.Google Scholar, 18Mahtani KR, Heneghan CJ, Glasziou PP, Perera R. Reminder packaging for improving adherence to self-administered long-term medications. Cochrane Database Syst Rev 2011; CD005025.Google Scholar] will improve patients’ adherence and also their disease progression. The importance of drug adherence should be openly addressed and combined with education and information on the disease and the rationale of treatment. Having identified this critical problem in the care of patients suffering from AIH, the study demonstrates that additional research is necessary to investigate the physician-related and disease-related factors having an impact on drug-adherence. Furthermore, studies examining interventions in order to improve adherence are necessary. Chronic diseases ask for patient autonomy and shared decision-making. Examining adherence openly in a non-accusing manner should be a routine part of every visit as well as identification of factors that may predispose for poor adherence – not only in patients suffering from AIH. Tackling these factors may be difficult and time-consuming but worthwhile, as there are multiple studies suggesting increases in drug adherence lead to possible reduction of total health care cost [19Roebuck M.C. Liberman J.N. Gemmill-Toyama M. Brennan T.A. Medication adherence leads to lower health care use and costs despite increased drug spending.Health Aff (Millwood). 2011; 30: 91-99Crossref PubMed Scopus (337) Google Scholar, 20Desborough J.A. Sach T. Bhattacharya D. Holland R.C. Wright D.J. A cost-consequences analysis of an adherence focused pharmacist-led medication review service.Int J Pharm Pract. 2012; 20: 41-49Crossref PubMed Scopus (24) Google Scholar] and hopefully also better patient-physician relationships as well as healthier patients. Conflict of interestThe authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript. The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.