From the American College of Gastroenterology Annual Scientific Meeting: Know your options for cost-effective management of HE


The economic implications of HE are numerous and marked altered as based upon direct and indirect costs, worsening of patient's and patient's family members quality of life, employment status, and autonomy.


Chronic liver disease affects more than 8 million people in the United States. The etiology of chronic liver disease ranges from infections, medications, inheritable disorders, and metabolic- and alcohol-related disease mechanisms. There are numerous liver-related problems as a consequence of chronic liver disease that can culminate into extensive damage, known as cirrhosis. Presently 800,000 to 1 million patients currently suffer from cirrhosis in the United States resulting in more than 30,000 deaths annually. 

 Of the numerous comorbid complications associated with cirrhosis, overt hepatic encephalopathy (HE), carries an ominous long-term survival, less than 50% at 12 months. HE is reflective of various levels of cognitive impairment and is commonly found in patients with cirrhosis and can lead to an overt event that requires hospitalization to recover.

The economic implications of HE are numerous and marked altered as based upon direct and indirect costs, worsening of patient’s and patient’s family members quality of life, employment status, and autonomy. One of the most expensive components when measuring cirrhosis economics is HE-related hospital admission and readmissions-up by 70% over the past 8 years. Additionally the cost has increased 80% to $37,598 over the same timeframe, yet the length of stays has stabilized at 6 days.1

Hepatologists struggle with the ongoing disease process of cirrhosis while patients await the possibility of liver transplant, the only cure, or likely death. The patients and their families are affected with the day-to-day management of a loved one suffering from alternating stages of cognizance, until transplantation or death.

There are a number of therapeutic medication options to abate HE and the associated memory changes. FDA has approved 3 therapies; neomycin, lactulose, and the most recent, rifaximin. Lactulose has been an effective HE therapy for the past 30 plus years for HE.  Recognition of lactulose-related side effects can affect quality of life and compliance, often resulting in poor disease control due to the daily drug dosage adjustments.2,3 Rifaximin (Xifaxan, Salix) 550 mg is another option that offers patients effective therapy with few, if any, side effects. As a result most patients prefer rifaximin and tend to remain more compliant on therapy, thus requiring less hospitalizations.4,5

Of importance is the combined economic downturn and increased number of patients with cirrhosis forcing physicians to evaluate economic-minded treatment algorithms. The medical community has historically been mindful of drug price and not cognizant of the economics of the entire disease spectrum; direct and indirect costs. Understanding not only drug costs but rather the overall disease process and economic impact has gained much needed attention. Additionally, traditional treatment protocols in all diseases continue to progress toward early disease recognition and intervention. However in patients diagnosed with cirrhosis and suffering from HE, physicians often allow for disease development culminating in a non-surprising poor 1-year survival rate of less than 50%.6 Thus therapeutic paradigm advances, disease frequency, hospitalizations costs, and disease awareness and prevention, are necessary components to consider when managing any disease process.

Length of hospital stay (LOS) and hospital readmissions are quickly becoming important economic parameters, including CMS milestones. In fact, CMS penalties are in place for readmission and likely forthcoming for patients with cirrhosis. Bundled reimbursements are forthcoming and will force the medical community to become mindful of shortened LOS and reductions in readmissions. During the recent American College of Gastroenterologists (ACG) meeting, numerous retrospective reports demonstrated improvements in various pharmacoeconomic patterns when comparing rifaximin, and lactulose.

Several reports, based upon research work done at Tampa General Hospital, were presented at the ACG 2012, and show the economic importance of preventing readmission and shortening LOS. Patients treated with rifaximin 550 mg twice per day were shown in monotherapy or combination therapy (rifaximin and lactulose) to have shortened LOS and reduced readmission frequency. Numerous issues account for the elevated readmission rates related to HE including noncompliance due to therapy intolerance, patient abstinence, in addition to disease progression, resulting in more frequent readmissions to the hospital.

Major cost benefits were found in the group with decreased LOS, shortened time to full diet, and reduced frequency of readmission (P=.038). Additionally this group treated with rifaximin benefitted despite having higher MELD (liver transplant score) scores. All in all, the results demonstrate the importance of evaluating economics of the disease spectrum, not limiting the focus to the drug costs but rather to the entire equation that includes all direct and indirect costs. As the healthcare system transforms into a payer system that will include primarily bundle reimbursements, lowering hospitalization frequency, the LOS will result in cost benefits to the hospital and clinical benefits to patients. ■


  • Agency for Healthcare Research and Quality. Healthcare Cost and Utilization Project. Available at Accessed February 15, 2013.

  • Bajaj JS, Wade JB, Gibson DP, et al. The multi-dimensional burden of cirrhosis and hepatic encephalopathy on patients and caregivers. Am J Gastroenterol. 2011;106(9):1646–1653. Epub 2011 May 10.

  • Sanyal A, Younossi ZM, Bass NM, et al. Randomised clinical trial: rifaximin improves health-related quality of life in cirrhotic patients with hepatic encephalopathy - a double-blind placebo-controlled study. Aliment Pharmacol Ther. 2011;34(8):853–861. Epub 2011 Aug 17.

  • Bass NM, Mullen KD, Sanyal A, et al. Rifaximin treatment in hepatic encephalopathy. N Engl J Med. 2010;362(12):1071–1081.

  • Neff G. Pharmacoeconomics of hepatic encephalopathy. Pharmacotherapy. 2010;30(5 Pt 2):28S–32S.

  • Bustamante J, Rimola A, Ventura PJ, et al. Prognostic significance of hepatic encephalopathy in patients with cirrhosis. J Hepatol. 1999;30(5):890–895.
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