Brief Overview of Non-Alcoholic Steatohepatitis (NASH) and Potential Future Treatments

Non-alcoholic steatohepatitis (NASH) is liver inflammation and damage caused by a buildup of fat. It is a more severe and progressive form of nonalcoholic fatty liver disease (NAFLD). While NAFLD has a relatively benign prognosis, NASH has a risk of progression to fibrosis, cirrhosis, and rarely liver cancer. About a quarter of patients with NAFLD progress to NASH. The major risk factors for NASH are obesity, type 2 diabetes mellitus, dyslipidemia, and metabolic syndrome. The prevalence of NASH is estimated at 1-5% of the population.  NASH is typically a silent disease in the early stages. It can take years or even decades for NASH to become serious enough to cause symptoms such as fatigue, weight loss, weakness, and right upper quadrant discomfort.

The gold standard for diagnosing NASH is liver biopsy, as this is the only test that can distinguish NASH from NAFLD. Considering the invasive nature of liver biopsy and the sheer number of NASH patients, routine use of biopsy will be financially challenging. Manufacturers and researchers are studying the accuracy and clinical utility of non-invasive diagnostic tools to more easily diagnose patients.

The treatment of NASH involves non-pharmacologic therapy including weight loss through exercise and dietary changes and a restriction in alcohol consumption. Currently, there are no FDA approved medications for NASH. However, efficacy has been demonstrated with pioglitazone and vitamin E, which are now used off-label.

With no medications approved for NASH, the pipeline is filled with potential agents exploring different mechanisms.  It is clear that manufacturers are in an exploratory phase of treating this condition.

For example, one of the early medications is obeticholic acid (OCA), a farnesoid X receptor inhibitor. This medication decreases liver bile acid build up, inflammation, and fibrosis of the liver. OCA is already approved for the orphan disease primary biliary colangitis (PBC), making NASH the second potential indication for OCA.

As new medications have been tested for NASH, defining the population that will benefit most from pharmacologic therapy has become increasingly important. Some clinical trials have a population consisting of all patients with NASH, while others have a population of patients with NASH and severe fibrosis. The FDA held a liver conference in 2013 and determined that the best patient population for NASH medications is those with NASH and a high fibrosis score. These patients are most at risk for cirrhosis and liver failure.

Treatments for NASH are expected to be a major focus once FDA approved products are on the market.  Start planning now for managing the expected new treatments for NASH.

Different Actions Targeting Opioid Abuse and Misuse

There are many different actions taking place to target opioid abuse and misuse.  PHSI regularly posts about the DEA Drug Take Back Days.  Prescription Drug Monitoring Programs enable healthcare providers to monitor patient use of opioids with the goal to reduce deaths due to opioid use.  Changes are being made to make naloxone available without a prescription through standing orders.  Physicians can now treat an increased number of patients with buprenorphine.  Another new solution on the horizon is an opioid deactivation pouch.  This product deactivates opioids by adding the tablets/capsules/liquid/patch, etc. to the pouch and adding water then disposing of the combination in the trash.  This simple process will enable patients and caregivers to safely dispose of opioid medications and provide another option beyond the drug take back programs. What do you think of the deactivation pouch?  In what situation would you think that the pouch would be helpful?

Connecting Patients with Mental Health Pharmacies

There are many different specialized pharmacies but this is a new unique specialization. A new website has launched to list and direct patients to 850 pharmacies that specialize in mental health pharmacy services. These pharmacies meet certain criteria to be listed and the website allows the patient to search for a pharmacy by address. This appears to be a nice way to help patients. Now the challenge is to get providers and patients to know about the website and use it! Would you recommend a patient use this website if the patient would transfer to another pharmacy? Will payers see the value in specialized services for certain populations? We welcome your thoughts through the comments section below or sending us a message.

Highmark Response to PPA Advocating

This summer, Highmark announced that the vaccine administration fee paid to pharmacies would be cut from $25 to $3.  The Pennsylvania Pharmacists Association (PPA) acted swiftly to address this 88% reduction in payment that could severely impact pharmacies throughout the Commonwealth.  PPA members and staff held a discussion with Highmark to highlight the concerns with such a drastic reduction in payment.  Highmark listened to their concerns, conducted research, and effective September 12, 2016, increased the administration fee they pay to pharmacies for all vaccines to $10.  While still a reduction compared to the earlier payment rate, the increase to $10 helps to account for the time and resources that pharmacies spend to provide vaccines to their patients.  Was Highmark’s response appropriate?  What is a fair administration fee to a pharmacy for providing an immunization?

Precision Medicine

What is precision medicine?

Precision medicine is a practice of individualizing medical treatment based on a variety of patient-specific characteristics, moving away from treatments based on the “average” patient.  Medical decisions are based on a patient’s genetics, disease characteristics, environment, and lifestyle.

Precision medicine vs. patient-centered medicine

Patient-centered medicine is the practice of individualizing medical care focused on involving the patient in treatment decisions.  Using patient-centered medicine, the healthcare professional will make a plan involving the patient’s needs, concerns, and preferences.  Precision medicine builds upon the patient centered foundation of behavioral and lifestyle aspects, but also incorporates physical, genetic, and environmental characteristics outside of the patient’s control to optimize treatment.

Precision Medicine Initiative

For precision medicine to be widely adopted and effective, the relationships between each patient characteristic (genetics, lifestyle, biological markers, activity, physiological measures, etc.) and their effects on a patient’s health needs to be understood.  The Precision Medicine Initiative, announced in the 2015 State of the Union Address, is a nationwide research effort to study a cohort of 1 million U.S. patients.  The initiative is still in its beginning stages and patient recruitment is ongoing.  In July 2016, Walgreens announced its patient enrollment efforts through in-person, online, and mobile app outreach.

The goals of the cohort program are:

  • Develop ways to measure risk based on environmental and genetic interactions
  • Identify causes of individual differences in response to medications
  • Discover biological markers that signal increased or decreased risk to develop diseases
  • Use of mobile health technologies to correlate activity, physiological measures and environmental exposures with health outcomes
  • Develop new disease classifications and relationships
  • Empower study participants with data and information to improve their own health
  • Create a platform to enable trials of targeted therapies

The Future of Precision Medicine

The future of healthcare is expected to be driven by precision medicine; elements of precision medicine, such as records in EHR and point-of-care testing, may impact future quality measures and provider reimbursement.  Pharmacists are expected to play a major role in patient monitoring, most obviously on medication adherence, outcomes, and adverse effects but could include genetics, lifestyle, and other health markers.

Reduced Opioid Manufacturing

The DEA plans to reduce the total opioid production in 2017. Could this be part of the strategy to squeeze the supply of opioid medications in the marketplace? The decrease may vary by product but the overall decline is about 25%.  This change seems large until learning that previous production levels included a 25% buffer to avoid drug shortages.  What are your thoughts about this reduction?  Will this have any affect on each of the different stakeholders? Is this part of the DEA’s strategy to combat opioid addiction in the country?  Will this situation drive more patients to seek illicit drugs?

Common Ground on Drug Pricing

The following linked article provides viewpoints from many different stakeholders regarding drug pricing.  One of the good discussion points includes that if a manufacturer brings a product to market, Medicaid will pay for it.  Americans drive innovation but just because something is available, does that mean the expectation is that it is covered by health insurance?  What are your thoughts on the societal issues around drug pricing? Will society continue to pay for drug innovation?

Drug Transparency Mandated in Vermont

Vermont became the first state to enforce drug pricing transparency from pharmaceutical companies. The bill took effect on June 2nd and requires manufacturers to be open about what goes into the pricing of their drug. The intent is for manufacturers to be held more accountable for their pricing. An act related to prescription drugs (Act no. 165) requires all factors contributing to a drug’s wholesale acquisition cost (WAC) increase to be disclosed.  Manufacturers must demonstrate what percent each factor is attributing to the change and an explanation of why the change has occurred. The Green Mountain Care Board, an independent group tasked with improving Vermont’s healthcare system, and the Department of Vermont Health Access will work together to compose an annual list of up to 15 high expenditure drugs. In order to qualify for this list, the drug’s WAC must have increased over 50% in the last 5 years or seen an increase of 15% over the last twelve months. If a manufacturer’s drug is selected they must justify this increase or face civil penalties of up to $10,000 per violation. Ultimately, the attorney general will collect the manufacturer’s information and publish a report on the board’s public website. To appease bill opponents, names of the drugs in question and their manufacturer will not be released. The bill also requires Vermont’s Medicaid program to use 340B pricing for reimbursement through qualifying health centers.

Health insurance companies must now provide more detailed information on projected prescription costs through their plans. This will be accomplished through online information such as the drugs covered by the plan, the applicable cost sharing amount, drug tiers, prior authorization and step therapy protocols, which is a standard met by Medicare Part D Plans today. These requirements must be met on or before January 1, 2017.

Lowering healthcare cost is at the forefront of many politicians’ minds. While price justification may be one tool to reign in rising expenditures, many question the practicality of the bill. Critics have highlighted that WAC does not usually represent what is being paid after rebates and has little influence on the price paid by patients. Others say that because of the various determinates of drug price such as research and development; transparency of drug prices is not as simple as it sounds. Much like gas or food products, drug prices are based upon changing variables and can often fluctuate depending on market share or drugs in production. Forcing manufacturers to keep drug costs fixed or down may cause less profitable research areas to lose funding. Alternatively some manufacturers could cease making a product, leading to shortages and potential price increases.

It is still unclear how pharmaceutical manufacturers will respond to Vermont. We doubt this new requirement will have any significant import on the overall cost of prescription drugs. It will take time to see how the bill affects its current healthcare system. States may choose to adopt similar bills if Vermont’s increased oversight of pharmaceutical manufacturers proves valuable. Certainly this will not be the last strategy proposed to slow healthcare spending and rising prescription costs.

View Vermont Act 165 at

DEA Drug Take-Back Day October 2016

The next National Prescription Drug Take-Back Day sponsored by the Drug Enforcement Administration (DEA) is scheduled for Saturday, October 22, 2016 from 10:00 am to 2:00 pm at participating locations. Search for a Drug Take-Back Day disposal site near you at

Bring your unused, expired, and unwanted medication to a site near you. It is important to dispose of medication properly to reduce the risk of harm from taking an expired medication, accidental exposure, and intentional misuse. Visit the DEA website at for more information on drug disposal.

The DEA typically sponsors two National Prescription Drug Take-Back Days per year, but you don’t have to wait for one of these events to safely dispose of your prescription drugs. There are many authorized collectors around the country that provide drug take-back services year-round.

Different medications can be disposed of in different ways. Most medication can be disposed of at registered take-back locations. Some locations may have individual limitations on medication that they can accept, but medications and supplies that should be excluded from this process include:

  • Needles and syringes
  • Diabetic testing supplies
  • IV bags and tubing
  • Biohazard material
  • Controlled substances (police stations may be able to handle the disposal of these medications)

To find a Controlled Substance Public Disposal Location near you, visit

Electronic smoking devices to be regulated by the FDA effective August 8, 2016

There are an estimated 5.5 million e-cigarette users in the United States.  First introduced to the US in 2007, e-cigarettes are electronic devices that look like cigarettes but atomize liquid into a vapor rather than burning tobacco.  The liquid comes in a variety of flavors and typically contains nicotine.  Most users believe that e-cigarettes are a safer alternative to tobacco cigarettes; this belief is supported by manufacturer marketing.  The vapors produced by e-cigarettes might very well be safer than tobacco smoke, but the data to support this claim is lacking.

A 2015 analysis of 42 common brands of e-cigarette refill liquids was completed by Varlet et al.  This study found that every product contained some measurable amount of potentially harmful compound.  Most of the refill liquids contain nicotine, diethylene glycol, ethylene glycol, ethanol, formaldehyde, and acrolein.  All compounds were within FDA limits, but the long term effect of chronic exposure to these remains unknown.1

E-cigarettes are not allowed to be marketed for smoking cessation, but that hasn’t stopped people attempting to quit smoking by turning to e-cigarettes for help.  A small number of studies have shown smokers reduce the number of tobacco cigarettes while using e-cigarettes, but these studies are old and have several limitations, including insufficient statistical power, unequal losses of participants to follow up, and the use of now obsolete e-cigarette brands.

More recently, a 2015 study conducted by Primack et al. demonstrated, in a longitudinal cohort study of 694 participants between 16 and 26 who never smoked, that use of e-cigarettes at baseline was associated with eventual use of tobacco cigarettes.2  At the start of the study, 2.3% of participants reported e-cigarette use, by the end of the study 70% of e-cigarette users were smoking tobacco cigarettes, compared with 20% of participants that did not use e-cigarettes at the start of the study.

Drawing from data available from the National Poison Data System, Kamboj et al. conducted a retrospective study earlier this year and found that from January 2012 to April 2015 the number of calls related to e-cigarette exposure in children 6 or younger increased from 14 reports in January 2012 to 223 reports in April 2015.  Further analysis showed children exposed to e-cigarettes had greater risk of hospitalization (5.2 times) and greater risk of severe medical outcomes (2.6 times) than those exposed to tobacco cigarettes.3

Effective August 8, 2016, e-cigarettes will be covered under the FD&C Act, as amended by the Family Smoking Prevention and Tobacco Control Act.  The FDA will regulate e-cigarettes the same as it regulates all other tobacco products.  E-cigarettes will no longer be available to purchase for people under 18 and packaging will be required to display the same health warnings as other tobacco products.4

While e-cigarettes might appear to be a safe, convenient alternative to tobacco cigarettes, and other tobacco products, the data continues to suggest that for the majority of patients they are not safe.  Beyond the known possible hazards of potentially toxic compounds, inconsistent quality control and labeling may create additional health risks.  The use of e-cigarettes for smoking cessation should not be considered unless a patient has failed several other proven, effective methods.  If a patient decides to use e-cigarettes, the risks and benefit should be discussed in detail and it should be communicated that e-cigarettes are not necessarily a safer alternative to tobacco cigarettes.



  1. Varlet V, Farallinos K, Augsburger M, et al. Toxicity assessment of refill liquids for electronic cigarettes. Int J Environ Res Public Health 2015;12:4796-815.
  2. Primack BA, Soneji S, Stoolmiller M, et al. Progression to traditional cigarette smoking after electronic cigarette use among US adolescents and young adults. JAMA Pediatr 2015;169:1018-23.
  3. Kamboj A, Spiller HA, Casavant MJ, et al. Pediatric exposure to e-cigarettes, nicotine, and tobacco products in the United States. Pediatrics Published online ahead of print, May 9, 2016. Doi:10.1542/peds.2016-0041.
  4. Food and Drug Administration, HHS. Deeming tobacco products to be subject to the Federal Food, Drug, and Cosmetics Act, as amended by the Family Smoking Prevention and Tobacco Control Acts; Restrictions on the sale and distribution of tobacco products and required warning statements for tobacco products. Final rule.  Fed Regist 2016;18:28973-9106.