Optimizing Medication Management for Patients With Cirrhosis

Evidence-Based Strategies and Their Outcomes

Mary J. Thomson; Anna S. Lok; Elliot B. Tapper

Liver International. 2018;38(11):1882-1890.

Abstract and Introduction

Abstract

Cirrhosis is a morbid condition associated with frequent hospitalizations and high mortality. Management of cirrhosis requires complex medication regimens to treat underlying liver disease, complications of cirrhosis and comorbid conditions. This review examines the complexities of medication management in cirrhosis, barriers to optimal medication use, and potential interventions to streamline medication regimens and avoid medication errors. A literature review was performed by searching PUBMED through December 2017 and article reference lists to identify articles relevant to medication management, complications, adherence, and interventions to improve medication use in cirrhosis. The structural barriers in cirrhosis include sheer medication complexity related to the number of medications and potential for cognitive impairment in this population, faulty medication reconciliation and limited adherence. Tested interventions have included patient self-education, provider driven patient education, intensive case management including medication blister packs and smartphone applications. Initiatives are needed to improve patient, caregiver and provider education on appropriate use of medications in patients with cirrhosis. A multidisciplinary team should be established to coordinate care with close monitoring, address patient and caregiver concerns, and to provide timely access to outpatient evaluation of urgent/complex issues. Future studies evaluating the clinical outcomes and cost effectiveness of interventions are needed.

Introduction

Cirrhosis is the end result of chronic liver disease. It affects over 600 000 adults in the USA, with estimates that an additional five million have at least bridging fibrosis.^[1,2] These numbers will rise as baby boomers with chronic hepatitis C age and the incidence of nonalcoholic fatty liver disease grows.^[3] Indeed, patients with cirrhosis seeking medical attention has increased by 59% over the past decade,^[4] and cirrhosis is now the 12^th leading cause of death in the USA.^[5] Compounding the problem of rising prevalence, cirrhosis is an expensive condition, with an estimated annual healthcare cost of $2 billion dollars in the USA.^[6]

The primary drivers of morbidity and cost in cirrhosis are complications of decompensated disease: ascites, hepatic encephalopathy (HE) and variceal hemorrhage. Patients are frequently hospitalized for these conditions, with high 30–day readmission rates ranging from 25%–52%.^[7,8] Providers prescribe a variety of medications with narrow therapeutic windows to treat these complications. Even for the most experienced provider, managing these medications is challenging. The risks of medication errors and serious side effects are magnified by difficulties with patient adherence, medication interactions, and the need for frequent dosage adjustments. Herein, we review the data on challenges and solutions for optimal medication management in patients with cirrhosis.

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Next Section

Abstract and Introduction
Methods
Complications of Medical Therapy
Structural Barriers to Optimal Medication Management
Interventions to Improve Medication Management
Conclusions
References
Sidebar

Table 1. Commonly used medications and adverse effects in cirrhosis
Medication class	Indication	Take home point	Adverse effects
NSAIDs	Acute and chronic pain	Readily available and often prescribed first line, but should not be used in the presence of ascites⁵⁰	AKI( )Gastrointestinal bleeding
Acetaminophen		Lower daily dose (≤2000 mg daily) is safe to use⁵¹ and preferred first line pain medication	Acute liver injury/failure with higher than recommended doses
Narcotics		Commonly prescribed (19%–60% of patients)^{52, 53}	Constipation HE Drug dependence
Proton Pump Inhibitors	GERD, PUD, dyspepsia	Long term PPI use is often not indicated, up to 63% of patients are continued on a PPI indefinitely after a variceal bleed²³	Potential association with Spontaneous Bacterial Peritonitis, HE^{10, 25} C. difficile infection²⁶
Statins	Cardiovascular risk reduction	Statins have been shown to be safe in compensated cirrhosis and should be continued as clinically indicated. Recent studies suggest they may be beneficial in patients with cirrhosis ^{54, 55}	Elevated liver enzymes (only clinically significant if bilirubin is elevated, which is rare)⁵⁴ Myalgias

AKI, Acute Kidney Injury; GERD, Gastroesophageal reflux disease; HE, Hepatic Encephalopathy; NSAIDs, Non-Steroidal Anti-Inflammatory Drugs; PPI, Proton Pump Inhibitors; PUD, Peptic ulcer disease.

Table 2. Medication adherence in the pre– and post-liver transplant patient population
Article	Patient population; n	Adherence measure	Significant findings	Affecting clinical outcomes?
Hayward 2016³²	Cirrhosis n = 50; 40% decompensated	Self-reported medication list compared to medical record	54% had ≥1 and 24% had ≥3 discrepancies between what patients were taking and the prescribed regimens	Not measured
Leevy 2007³⁵	Hepatic encephalopathy n = 145; 95% with cirrhosis, 12% on transplant list	Retrospective review of medical record	92% took rifaximin for >75% of prescribed doses 30% took lactulose for >75% of prescribed doses	Fewer hospitalizations and hospital days when patients were taking rifaximin
Polis 2015²⁸	Cirrhosis, n = 29; mean MELD 11	Patient response (MMAS–8)	54% "sometimes forgot to take their medications" in the past 30 d 29% had missed 1 or more medication over the last 2 wk	Not measured
Kuo 2016¹³	Patients listed for liver transplant, n = 181; mean MELD 13	Patient response (MMAS–8)	42% "sometimes forgot to take their medications" 28% missed 1 or more medications in the past 2 wk 12% missed 1 or more medications in the day prior	Not measured
Serper 2015⁵⁶	Liver transplant recipients, n = 105; median 20 mo from transplant	Structured interviews to determine patient knowledge and self-reported use compared with medical record abstraction and tacrolimus blood levels	86% displayed correct medication treatment knowledge 78% could demonstrate simulated regimen use to researchers 14% self-reported as non-adherent 32% non-adherence based on tacrolimus levels	Higher treatment knowledge scores and demonstrated regimen use associated with reduced readmissions after liver transplant

MELD, Model for End-Stage Liver Disease; MMAS–8, Morisky Medication Adherence Scale.

Table 3. Interventions in medication management
Article	Domain	Intervention	Population; n	Process Measure	Process measures/Improved clinical outcomes?
Volk 2013⁴¹	Patient self-management	Educational booklet	Cirrhosis; 150;70% Child A cirrhosis	Cirrhosis knowledge survey at baseline and at 3 mo	Median knowledge increased/not evaluated
Larrey 2011⁴⁰	Nursing led education	Scheduled nurse clinic visits	CHC; 244; 29.4% F3–4 fibrosis	Adherence, SVR	48–week adherence improved/Higher SVR in treatment group
Asavakarn 2016⁵⁷	Pharmacy led, multidisciplinary team educational approach	Education during hospitalization for LT and initial follow-up visit	LT recipients; 50; 64% ≤3 mo post LT	Immunosuppressant knowledge questionnaire	Improved knowledge/not evaluated
Promraj 2016⁵⁸	Pharmacy led, multidisciplinary team educational approach	Education during hospitalization for LT and initial follow-up visit	LT recipients; 50;64% ≤3 mo post LT	Immunosuppressive Therapy Adherence Scale	Higher medication knowledge scores correlated with higher ITAS/not evaluated
Russo 2016⁵⁹	Multidisciplinary protocol to reduce readmissions	Outpatient service expansion, Pharmacist teaching	LT recipients; 167; mean MELD at LT 21	30–day readmission Length of stay for index admission for liver transplant	30–day readmission rate/30–day readmission rate decreased
Wigg 2013⁴²	Chronic disease management program	Delivery system redesign Self-management support Protocol driven decision support Clinical information systems	Cirrhosis with ascites; 40; mean MELD 11	Days hospitalized for liver related reasons Attendance to outpatient clinic visits Quality of care measures	Improved clinic attendance, Hepatocellular carcinoma screening rates, referral for LT, and Hepatitis A/B vaccination Did not reduce days hospitalized for liver related reasons or all cause admission rate
Ganapathy 2017 ⁴⁵	Smart phone App to reduce readmissions	Smart phone app to track medications, sodium intake, daily weight, signs of HE Patient and caregiver education Enhanced communication with health care team	Decompensated cirrhosis; 40; mean MELD 19.5	30–day readmission Medication adherence Contact with study team	No 30–day readmissions for HE App was tolerable for patients and caregivers

CHC, Chronic Hepatitis C; HE, Hepatic Encephalopathy; ITAS, Immunosuppressive Therapy Adherence Scale; LT, Liver Transplant; MELD, Model for End-Stage Liver Disease; SVR, Sustained Virological Response.