COMMENTARY

GI Practice Updates for Primary Care Providers

Digestive Disease Week (DDW) 2015

David A. Johnson, MD

Disclosures

July 02, 2015

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Hello. I'm Dr David Johnson, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School.

Welcome back to another GI Common Concerns -- Computer Consult. Rather than focus on a single topic this time, I've decided to shake things up a little bit and give you my perspective on some hot topics from Digestive Disease Week (DDW) 2015, one of our two national gastroenterology meetings, that are applicable to primary care providers. This new information could change your practice and the way you counsel your patients.

Celiac Disease

The first hot area is about celiac disease. Many of you probably recommend probiotics, or have your patients come in and say, "I'm taking a probiotic." Dr Peter Green, part of a research team from Columbia, presented research[1] comparing the gluten component of 22 probiotics. They did liquid chromatography/mass spectrometry analysis to determine the gluten component of the probiotics.

Of the 22 products tested, 15 (68%) were labeled "gluten-free." The researchers found that 12 of the 22 probiotics contained gluten. Of those 12, 67% were actually labeled "gluten free." So, we may be prescribing or recommending probiotics that have a high concentration of gluten to our patients with celiac disease. The study found that of the 15 probiotics labeled "gluten-free," 53% contained gluten, and two had high levels of gluten (more than 20 parts per million).

This tells us that we need to be careful about probiotics in patients with celiac disease. We're recognizing that gluten enteropathy occurs not only in people with celiac disease, but also in those who have gluten sensitivity, and some probiotics may be doing harm.

Another presentation[2] on celiac disease looked at fecal elastase, which is measured during evaluation or monitoring of pancreatic insufficiency. When doing an initial workup on a patient with diarrhea, we check a gluten panel and a pancreatic elastase level, and the results can suggest pancreatic insufficiency.

This group evaluated patients with celiac disease and identified 10 patients with pancreatic insufficiency using fecal elastase. When their celiac disease was treated with a gluten-free diet, seven patients responded well and had follow-up pancreatic workups; in the second evaluation, the pancreatic insufficiency was resolved. So be careful when you start ordering these tests, and presume that you may have two diseases.

Eosinophilic Esophagitis

Eosinophilic esophagitis is something that you are seeing increasingly more of from referring gastroenterologists. A group from Chapel Hill in North Carolina[3] looked at steroid treatment vs a six-food elimination diet (now the standard of care) for treatment of eosinophilic esophagitis. The six-food elimination diet removes gluten, milk, eggs, soy, shellfish, and peanuts. These foods are removed entirely and sequentially reintroduced. This has proven to be (at least on a modeling basis) far more effective than inhaled and swallowed steroids.

Remember the term "six-food elimination diet." It showed very favorable results in this study.

Gastroesophageal Reflux Disease

Alginic acid (alginate), something we have used for a long time, is a seaweed product that basically forms a mechanical raft on top of the gastric fundic pool to create an antacid effect. It's a treatment that goes back to the 1980s, and I use it often in my pregnant patients.

A prospective, randomized trial[4] from Europe looked at alginate in addition to a proton pump inhibitor (PPI) in gastroesophageal reflux disease (GERD). Many of you in primary care deal with the PPI "partial responder," and alginate suspension (Gaviscon) has a highly significant adjunctive benefit in these patients. These researchers studied alginate as an add-on treatment in patients with nighttime heartburn symptoms, and the results were highly statistically significant.

It may be easy to add this drug before referring patients. An alginate raft, in addition to a "don't eat late" recommendation, is very helpful.

Another topic important in GERD is the allegation of bone harm from PPIs. I'm sure that you get questions from your patients, because retrospective studies have made allegations of such harm as hip, cervical, and radial fractures.

Laura Targownik from Canada has done some seminal work on this, looking at longitudinal studies with balanced patient populations, and showing no harm. She did a study[5] of bone structure and metabolism, comparing long-term PPI use with no PPI use. Her group evaluated 104 patients: 52 in each group. They looked at bone metabolism parameters and did a very sophisticated analysis of bone structure from quantitative CT scans. At the end of an extended period, the study found no meaningful differences in volumetric bone mineral density in patients who had PPI exposure.

I tell my patients, "We need to talk about this. If you don't need calcium, you shouldn't take it." Now, you don't need to do specific bone density evaluations, but it is reasonable to discuss these issues with a patient who has PPI exposure—not because of risk but to inform, and because the internet can be a dangerous thing.

There was also a very interesting study presented by Bob Ganz[6] looking at the LINX procedure (LINX® Reflux Management System; Torax Medical, Inc.; Shoreview, Minnesota), in which a mechanical ring (called a magnetic esophageal device) is attached to the lower esophagus. This surgery requires the expertise of a foregut surgeon or a specialist in general surgery who is trained in foregut surgery. The device allows for adequate relaxation after patients swallow or when they try to belch or vomit.

The study did not look at long-term effects, but they do have long-term data (5 years). On study entry, 100% of the patients were on PPIs, but only 15% were on PPIs at 5 years. None showed significant problems with regurgitation, which I thought was really important, because regurgitation is something that we don't treat effectively with medical therapy. Although 57% had regurgitation on presentation, only 1.5% had it after 5 years. I would advise making sure that the surgeon is well-trained, and work with a gastroenterologist before sending the patient to surgery.

Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is something that we are seeing with increasing frequency. The advanced stages of disease lead to fibrosis and progression to cirrhosis. In the next 10 years, NAFLD will probably become the number one indication for liver transplantation. When hepatitis C is cured, we want to prevent cirrhosis in those patients, and this is something we don't necessarily do a good job of right now.

A prospective pilot study[7] looked at NAFLD screening with MRI and magnetic resonance elastography (MRE) at the primary care level. They performed a cross-sectional analysis of 100 patients with type 2 diabetes. These patients had no significant known liver disease, but the metabolic syndrome was evident in about 70% of them, and 66% had hypertension. Their body mass index (BMI) averaged 30 kg/m2. But on MRE, 65% of the patients had NAFLD and 7.1% had fibrosis.

So, we may start screening for NAFLD at the primary care level, and then those patients are referred to a gastroenterologist for further evaluation and intervention. It should not be dismissed. Elevated liver enzymes are not the only indication of liver disease. Many people in this group have normal liver enzymes.

Hepatitis C

I hope you are aware of the Centers for Disease Control and Prevention (CDC) recommendation to screen for hepatitis C virus (HCV) infection, especially in the baby boomer population.

A retrospective cohort study[8] from the Kaiser Permanente Group in California looked at an 11-year database evaluating patients with HCV infection. They looked at the number of patients who had HCV that progressed to liver disease and then to cirrhosis (23%), and the proportion of those with decompensated cirrhosis (27%). The numbers are pretty strong in favor of the need for awareness and intervention. We need to prevent and treat when we can, especially in patients with advanced fibrosis and cirrhosis.

I invite you to investigate a website that I was made aware of by Dr Paul Martin at DDW. It is the American Association for the Study of Liver Disease (AASLD) and the Infectious Diseases Society of America's recommendations for testing, managing, and treating HCV, a meaningful document that is updated live (meaning that it's a dynamic document) and is very helpful with respect to HCV.

Hepatitis B Reactivation During Chemotherapy

Moving to hepatitis B infection, there are two things that I want to bring to light.

One is poor compliance with surveillance recommendations. We know that hepatitis B virus (HBV) infection is a strong indicator for progression to hepatocellular carcinoma, but it is very uncommon that patients have surveillance in compliance with national guidelines. This evaluation[9] looked at adherence to AASLD's HBV guidelines,[10] finding that whether in primary care or gastroenterology practice, only one fifth of patients without cirrhosis and one third of those with cirrhosis received surveillance with optimal adherence to these guidelines. The current guidelines recommend ultrasonography every 6 months and consideration of an alpha-fetoprotein level (which is not a very good predictive test), but at least the ultrasonography should be done.

To build on that, I want to make you aware of poor compliance in the management of another high-risk population: patients with HBV infection who are undergoing chemotherapy. We have been aware of the relative risk in patients taking Rituxan® (rituximab) and, in particular, patients with malignancies such as lymphoma. We are also recognizing that there is a significant risk for reactivation of HBV infection in chemotherapy patients with solid malignancies. A retrospective evaluation (a meta-analysis and systematic review)[11] found that there is also a highly significant risk for HBV reactivation in people receiving other forms of immunosuppression and chemotherapy.

As an aside, our oncologists are pretty good at evaluating this risk with some chemotherapy agents, but for patients receiving solid-tumor therapies, we need to be on guard in primary care. You need to be asking the right questions and be a patient advocate. Make sure that patients have been screened for HBV; this includes HBV surface antigen and core antibody, because the core antibody reactivation is really the key. It is important that these patients have the appropriate follow-up.

A fantastic document by the American Gastroenterological Association[12] offers guidelines with specific reference to HBV reactivation and screening. This is something that oncologists are not quite on board with yet, but need to be. I've shared this with our oncologists, and some of them have said, "Wow!"

Irritable Bowel Syndrome

We know there are many reasons that physiologically, patients may have irritable bowel symptoms. There could be alterations in gut immunity or the microbiome, or changes in sensation, motility, secretions, metabolism, or digestion. All of these have been proposed as theories of irritable bowel syndrome (IBS).[13]

An L-menthol product, the main constituent of peppermint oil, has been proposed as a therapy for IBS. This is a new enteric formulation. Peppermint oil is an antispasmodic and antinausea agent, as well as a topical analgesic. It has some anti-infective potential and is a 5-HT3 receptor antagonist. These are all beneficial effects in a patient with IBS.

A 4-week, randomized, placebo-controlled study with 72 patients produced two abstracts[14,15]—and compared with placebo, peppermint oil improved virtually all of the patients' symptoms, including abdominal pain, bloating, and issues related to gas passage or incomplete evacuation. The treatment, a peppermint oil sold as IBgard®, is a food additive. It's commercially available in drugstores and is something you may want to consider recommending.

Gastrointestinal Bleeding

Another area that primary care providers may be involved in is trying to mitigate the outcomes of gastrointestinal (GI) bleeding in patients who have ulcers, significant arthritis, or cardiovascular risk.

This was a fantastic study.[16] It was an 18-month, double-blind, randomized controlled trial by Francis Chan, one of the world's recognized experts in the field. He has published several articles on this topic in the New England Journal of Medicine. [17,18,19,20] In this case, he looked at patients with high cardiovascular and GI risks (arthritis and cardiothrombotic disease) and, in particular, those with a history of ulcer bleeding. They randomly assigned the patients to receive either a cyclooxygenase-2 (COX-2) inhibitor (celecoxib) and a PPI, or naproxen and a PPI. Most patients (71%-72%) received low-dose aspirin.

The intention-to-treat analysis showed that patients with cardiothrombotic disease and a history of ulcer bleeding were better served by the COX-2 inhibitor and PPI combination than the nonselective nonsteroidal anti-inflammatory agent and PPI. The risk reduction rate was in excess of 55%.

When cardiothrombotic risk and GI bleeding in patients with arthritis was examined, a COX-2 inhibitor plus a PPI and, if needed, a cardiac dose of aspirin seemed to be associated with the best outcome. We will wait for the manuscript, but it's a no-brainer from my standpoint: This is the way to go for a high-risk patient.

Diverticulitis

Diverticulitis is another condition that we see a lot in practice. Approximately 50% of patients over age 50 years and 60% over age 60 years have diverticulosis. The lifetime risk for diverticulitis is about 4%, but it clearly does occur. So what do you tell your patients after they have had an event?

A study from the Mayo Clinic[21] conducted in Olmsted County looked at recurrent diverticulitis. They looked at 635 patients over a 27-year period who had one, two, or three episodes of diverticulitis. The results showed that after an initial diverticulitis episode, the recurrence rate at 1 year was 8%; at 5 years, 17%; and at 20 years, it was 22%. If a patient had a second episode, the 1-, 5-, and 10-year recurrence rates were 19%, 44%, and 55%, respectively. A limited number of patients had a third episode, and their recurrence rates were 24% at 1 year and 40% at 3 years.

These numbers will help you to counsel your patients. I would consider surgical intervention at some point in patients who have a consolidated area of diverticulitis that is well defined, especially if that area has been responsible for a relapsing course. There is nothing we can do from a diet or mechanical standpoint. I don't counsel patients that they need to avoid nuts or seeds, because it doesn't make sense.

Mental Health Concerns

I wanted to discuss the topic of mental health issues, which are often missed by specialists, and we need your help.

One study[22] was on the rate of mental disorders among high-risk patients with inflammatory bowel disease (IBD). I'm speaking here as a gastroenterologist, but I don't think we do a good enough job of recognizing or screening for mental health disorders. This study looked at the evaluation of mental disorders, defined as adjustment disorders (including anxiety), mood disorders, substance and alcohol abuse, psychosocial trauma, and schizophrenia. They found a 1.5-2 times higher rate of these mental disorders in patients with IBD.

As you see your patients with IBD (Crohn disease and ulcerative colitis) who are being managed by a gastroenterologist in your office, maybe you can help by screening these patients for mental health concerns and asking these questions. This is needed, and I don't think we are doing a very good job on the gastroenterology side.

Fecal Incontinence

Fecal incontinence is a real problem. If you look at the overall incontinence rates in noninstitutionalized US adults, they account for 9% of the population. Fewer than 30% have disclosed this symptom to their primary care provider or gastroenterologist. It is incumbent on us to ask about fecal incontinence.

A group at Chapel Hill did a survey on this.[23] They hired a group to look at people who had reported incontinence and asked, "How often have you discussed this with your physician?" Of the 234 respondents, less than one third had ever discussed it with their physician. The primary reason was embarrassment. The mean age of the population studied was 48 years (range, 20-91 years). This means that many people in their late 40s are having some incontinence that is not being discussed.

As a primary care provider, when you take a bowel history, ask more questions. I don't normally use the word "incontinence." I say "fecal leakage" or "seepage," which is a good way to start the conversation. It is something to build on. Recognize that these patients may need further evaluation, such as specific evaluations for pelvic floor dysfunction or interrectal motility. There are a variety of emerging tests or therapeutic interventions, which a gastroenterologist can help you with, but not unless you ask the right questions. You can at least get patients to the next level of testing.

As a primary care provider, it's important to know what is going on at the national specialty meetings, and I have tried to discuss items from DDW that I thought would be helpful to primary care providers. Gastroenterologists need your help. Some of these issues are pleas for primary care providers to at least help us become a better team and work together.

I'm Dr David Johnson. Thanks again for listening. I look forward to engaging with you again in the near future.

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