Impact of Kasai Portoenterostomy on Liver Transplantation

Posted on August 5, 2015 by gutsandgrowth

Briefly noted: JS Neto, et al. Liver Transpl 2015; 21: 922-7.

This retrospective cohort study of 347 biliary atresia patients who underwent liver transplantation )LT) (1995-2013) divided patients into eraly Kasai failures (K-EF) (27%), late Kasai failures (K-LF) (33%), and no Kasai portenterostomy (No-K) (40%). K-EF was defined by patients who underwent LT before 12 months of age.

Key findings:

After adjustment of confounding factors, the K-LF group had an 84% less probability of dying and 55% less chance to undergo retransplantation.
Having a K-EF did not have an effect on patient or graft survival compared to No-K.
Both the K-LF and K-EF had more post-LT biliary complications.

Bottomline: This retrospective study suggests that if a Kasai portoenterostomy helps postpone LT then this results in improved outcomes; whereas if it is ineffective, it does not impact survival compared to those who did not undergo a Kasai.

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From Cascade Canyon, Grand Tetons

Looking Twice for Eosinophilic Esophagitis

Posted on August 4, 2015 by gutsandgrowth

Not only do you have to take a lot of esophageal biopsies, now you may need to call your pathologist to make sure you do not miss a case of eosinophilic esophagitis (EoE), especially if there are mildly increased eosinophils. At least, that’s the message I inferred from a recent study (Rothenberg ME, et al. JPGN 2015; 61: 65-8).

In this study, the researchers identified 477 biopsies from 429 patients with EoE; 316 were from “PPI confirmed patients.”

Key finding: Of the 477 biopsies, 106 had a peak count of between 1 and 14 eos/hpf cited in the pathology report. However, 23/106 (22% with 1-14 eos/hpf) had ≥15 esos/hpf after a second review.

Overall, 5% of the 477 biopsies were mischaracterized as not meeting the threshold of ≥15 esos/hpf prior to review. Given this frequency at a major medical center and frequent referral center for EoE, my suspicion is that the yield of a 2nd look would be at least as high in most other centers.

Take-home point: Look twice for EoE if eosinophil count is between 1/hpf and 14/hpf. Maybe some new diagnoses are being missed and maybe some of your EoE patients in histologic remission really aren’t.

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Grand Tetons from Jenny Lake

Understanding the Problem Physicians Have With Retail Clinics

Posted on August 3, 2015 by gutsandgrowth

Two articles highlight the upside and downside of retail clinics.

Iglehart JK. NEJM 2015; 301-3
Chang JE et al. NEJM 2015; 382-8

Currently, there are ~1900 retail clinics with four main ‘players:’ CVS, Walgreens, Kroger, and Target. However, Target has recently made a deal with CVS and Walmart is expanding into retail clinics as well. Almost all of these clinics accept private insurance and medicare; growing numbers accept medicaid too.

Retail clinics offer a limited scope of care and typically are staffed by midlevel providers (nurse practitioners or physician assistants). In contrast, urgent cares offer more complex services and typically are staffed by physicians.

Upside:

For consumers, the key advantages of retail clinics: lower costs with transparent pricing, convenience due to extended hours and locations, and often short wait times.

Downside:

Potential disruption in longitudinal care (“medical home”)

What about quality?

“Research has not found that retail clinics deliver poor quality care, overprescribe antibiotics, or adversely impact delivery of preventive care.”

Do Retail Clinics Enhance Access?

Yes but these clinics are disproportionately located in areas with relatively high income. Nevertheless, “approximately 61% of retail-clinic visits and 37% of urgent care visits involve patients without a primary care provider.”

Patient navigation:

“One study …showed that patients did properly self-triage, with more than 88% of retail-clinic episodes resolved in one visit. Another study showed that 2.3% of retail-clinic patients were triaged to an emergency department or physician’s office.”

Why Would Physicians Oppose These Retail Clinics?

While primary care organizations have raised concerns about quality and continuity of care, a basic economic issue is likely at work as well. “The current reimbursement system renders simple acute health problems high-margin work that can offset losses from treating more complex problems.“

Bottomline: Retail clinics are filling a need for many patients in terms of cost and convenience for simple acute problems.

Related blog post: AAP -Behind the Scenes (Part 1)

Leek’s Marina, Grand Tetons

Intervention in Gallbladder Disease

Posted on August 2, 2015 by gutsandgrowth

A recent review (Baron TD, et al. NEJM 2015; 373: 357-65) provides a useful review of surgical and interventional approaches to gallbladder disease.

One recommendation in particular caught my attention:

“Recent data favor early laparoscopic cholecystectomy over medical management with delayed cholecystectomy. In one randomized trial involving patients with uncomplicated acute cholecystitis, laparoscopic cholecystectomy, when performed within 24 hours after the onset of cholecystitis, significantly reduced morbidity, length of hospital stay, and costs without increasing the need for conversion to open surgery.” (References: JAMA Surg 2015; 150: 129-36, Ann Surg 2013; 258: 385-93)

The authors’ Table 1 provides diagnostic guidelines and disease severity guidelines.

Grade 1 (mild): acute cholecystitis in otherwise healthy patient with mild local inflammatory changes and without organ dysfunction
Grade 2 (moderate) any of the following: leukocytosis >18K, palpable tender mass in RUQ, symptom duration >72 hr, marked local inflammation (gangrenous or emphysematous cholecystitis, pericholecystic or hepatic abscess, biliary peritonitis)
Grade 3 (severe) any of the following: hypotension requiring dopamine or norepinephrine, decreased consciousness, hypoxia, oliguria or creatinine >2.0 mg/dL, INR >1.5, or platelet count <100K

The review highlights the NOTES procedure, percutaneous cholecystotomy, and peroral endoscopic drainage (transpapillary vs. transmural).

Related blog post: Early Surgery For Acute Cholecystitis

Grand Tetons from Jackson Lodge

Celiac Disease and Neuropathy

Posted on August 1, 2015 by gutsandgrowth

From GI & Hep News: Celiac Disease Associated with 2.5-fold Risk of Neuropathy

Here’s an excerpt:

The use of Swedish population registries enabled first author Dr. Sujata P. Thawani of Columbia University, New York, and her colleagues to find that the risk of neuropathy was increased both before and after a diagnosis of celiac disease (CD).

“We found an increased risk of neuropathy in patients with CD that persists after CD diagnosis. Although absolute risks for neuropathy are low, CD is a potentially treatable condition with a young age of onset. Our findings suggest that screening could be beneficial in patients with neuropathy,” they wrote (JAMA Neurol. 2015 May 11 [doi:10.1001/jamaneurol.2015.0475]).Neuropathy has a known association with CD, an immune-mediated disorder characterized by sensitivity to gluten with an incidence of about 1% in Western Europe…

Dr. Thawani and her associates used Swedish pathology registers to identify individuals whose small intestine biopsies showed villous atrophy between 1969 and 2008 (Marsh stage 3, n = 28,232)…Each CD patient was matched with up to five age- and sex-matched controls (n = 139,473) from the Swedish Total Population Registry, all of whom were diagnosed in the same year and were from the same county as the matched CD patient.

Although 41.7% of CD patients were diagnosed in childhood, the median age at diagnosis was 29 years…

Surveillance bias may account for some of the increased risk for neuropathy…Notably, though, patients with a prior neuropathy diagnosis also were more likely to be diagnosed with CD, showing a bidirectional relationship.

Grand Tetons

Rejected! Most Stool is Not Good Enough for FMT

Posted on July 31, 2015 by gutsandgrowth

I found a recent study (Paramsothy S. Inflamm Bowel Dis 2015; 21: 1600-06) interesting in that it shows how few individuals would qualify as long-term stool donors for fecal microbiata transplantation (FMT). In previous discussions with colleagues, I’ve thought that getting paid to donate stool would be a pretty sweet deal.

In this study, the authors examined 116 potential donors. The donor screening protocols and donor inclusion/exclusion criteria were similar to many others (outlined in their Tables 1, 2 and 3 & noted in previous gutsandgrowth blog post on FMT). What the researchers found is that 47 prospective donors declined to participate after learning the requirements and only 12 of the remaining 69 (17%) remained eligible after concluding screening; this represents only 10% of the initial cohort. A large proportion of healthy asymptomatic donors failed stool testing –40% of those tested. The next most common reasons for rejection were medication comorbidities (n=13) or risk factors for Creutzfeldt-Jakob disease (n=6).

Bottomline: Now, I realize how these stool donors should be justifiably proud of their carefully-balanced uncontaminated microbiome. The difficulty in identifying suitable donors further reinforces the value of human stool banks.

Briefly noted:

Vandenplas Y, et al. “Fecal Microbiota Transplantation: Just a Fancy Trend? JPGN 2015; 61: 4-7. Brief overview which includes screening protocol used in Brussels. One of the recommendations is to conserve a sample of the donated stool for >30 years.

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Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist. This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Cumberland Island -Main Road

Not Using and Stopping Therapy in IBD

Posted on July 30, 2015 by gutsandgrowth

Two recent articles show that a lot of patients are not receiving much therapy in inflammatory bowel disease.

Moreno-Rincon E et al. Inflamm Bowel Dis 2015; 21: 1564-71.
Melesse DY et al. Inflamm Bowel Dis 2015; 21: 1615-22.

In the first article, a multicenter retrospective study of 102 patients, the authors examined the relapse rates of patients with ulcerative colitis who had withdrawal of thiopurines. They defined “significant clinical relapse” (SCR) as “the occurrence of UC typical signs or symptoms requiring a rescue therapy such as oral or intravenous corticosteroids, biological therapy, immunosuppressant drugs, recapture with TP [thiopurine] or surgery.”

Key findings:

Overall SCR was 32.35%.
Predictors of relapse included pancolitis (HR 5.01) and duration of treatment with thiopurines (HR 0.15).

Among those without relapse, the mean duration of remission prior to withdrawal of thiopurines was 54 months compared with 34 months in those who relapsed. In figure 2, the authors note that the rate of relapse was 19.2% for those who received >48 months of thiopurine treatment compared with a 45% rate of relapse for those who received treatment for 13-47 months. The authors note that several studies have shown higher relapse rates than reported in this cohort and that interruption of therapy is associated with a considerable risk of relapse.

Limitations: small retrospective study and the expectation that their SCR would capture the true relapse rate.

The second study, using a Manitoba database, shows a strikingly-high rate of nonuse of medical therapy. Between 1996-2012, 3902 patients with IBD were identified; 47% with Crohn’s disease (CD) and 53% with ulcerative colitis (UC). While only 11.7% of IBD patients did not have medication dispensed in the first year after diagnosis, beyond this period, “roughly half of all patients with IBD have not used IBD-specific medications in the previous year.” The authors are not certain how much nonuse is due to nonadherence or nonprescription. They note that there was higher nonuse in patients with CD, possibly due to use of surgical treatment. However, they note that multiple medications have been shown to reduce postsurgical relapse in CD.

My take: There are a lot of patients off therapy, both due to withdrawal of therapy when doing well and others due to nonadherence or nonprescription. With or without overt symptoms, these studies make one wonder whether undertreatment will lead to long-term complications or whether there could be a significant number of patients who are overtreated. Either way, it remains quite difficult to predict which patients will do well off medical therapy.

Broadcasters Really Know the Key Points to Winning!

What HBV Testing is Needed Before Tumor Necrosis Factor Inhibitor Therapy

Posted on July 29, 2015 by gutsandgrowth

As noted in a previous blog post (What’s Going on with Hepatitis A and Hepatitis B?):

Hepatitis B Reactivation risk & recommendation: (For all of the specifics — Full text article link)

High risk of reactivation (>10%): B cell depleting agents (eg. rituximab, ofatumumab), anthracycline derivatives (eg. doxorubicin, epirubicin), and daily moderate to high dose steroids (>10 mg) for at least 4 weeks. Recommendation: Use HBV prophylaxis
Moderate risk of reactivation (1-10%): anti-TNF therapy, integrin inhibitors (eg. ustekinimab, vedolizumab), tyrosine kinase inhibitors, low-dose steroids daily (<10 mg/day) for at least 4 weeks. Recommendation: Use HBV prophylaxis if HBsAg-positive but not if only anti-HBc-positive
Low risk of reactivation (<1%): azathiopurine, 6-mercaptopurine, methotrexate. Recommendation: No antiviral prophylaxis required.

For those interested in a more detailed summary of the recommendations: AGA Website HBV Reactivation Recommendations

In line with the reactivation risk, a new study (and editorial) (M Barone et al. Hepatology 2015; 62: 40-6; editorial BP Perillo. Hepatology 2105; 62: 16-8) indicates that for those receiving tumor necrosis inhibitor (anti-TNF) monotherapy, hepatitis B screening requires only checking HBsAg. The study examined a total of 1218 Caucasian rheumatologic patients (receiving biologic agents) between 2001-12. In this cohort, the authors identified 179 patients who had a previously resolved HBV infection; 146 treated with anti-TNF, 14 with rituximab, and 19 with other biologic therapy. Key finding: HBV reactivation was not seen in these patients.

Bottomline: For most pediatric patients receiving anti-TNF monotherapy (eg. infliximab, adalimumab), screening with HBsAg alone should suffice.

Grand Tetons from Jackson Lodge

Is It Right? Anti-TNF Therapy Does Not Fix IBD-Related Anemia

Posted on July 28, 2015 by gutsandgrowth

A surprising study (Koutroubakis, IE et al. Inflamm Bowel Dis 2015; 21: 1587-93) of prospectively-collected data from 430 patients with inflammatory bowel disease (IBD) showed that the rate of anemia did not change after 1 year in patients treated with anti-tumor necrosis factor (anti-TNF) therapy and oral iron.

The data was derived from 2010-2012 and included 324 patients with Crohn’s disease (51.6% females) with a median age of 41 years. Anemia was defined as hemoglobin (Hb) <13 g/dL in men and <12 g/dL in women. Patients with Hb <10 g/dL were considered to have severe anemia. Key findings:

Prevalence of anemia in IBD patients treated with anti-TNF was 38.1% at baseline and then 36.6% at 1 year.
Severe anemia was identified in 10% at baseline and 9.9% at 1 year.
A hematopoietic response with a Hb ≥2 g/dL was observed in 33.6% (n=45 of 134 anemic patients) and 14 (40%) of those with severe anemia.
There were 45 new anemic patients at 1 year; 64.4% were nonresponders to anti-TNF treatment.
Using multivariate logistic regression analysis, the author noted that use of immunomodulators was associated with an odds ratio of 2.56 of improvement in hemoglobin levels.

The authors state that anemia is the most common extra intestinal manifestation of IBD and remains underappreciated. Anemia in IBD correlates with the extent of intestinal disease and activity.

Bottomline: “Use of anti-TNF therapy had only a modest effect on patients’ Hb level.”

From related post: IBD Update January 2015 (Part 2)

Inflamm Bowel Dis 2014; 20: 2266-70. This study with 749 patients from Sweden showed that a large number of inflammatory bowel disease patients did not receive with iron supplementation: “Only 46% of patients with anemia were treated with iron supplementation or blood transfusion.” This study showed frequent persistence of anemia one year after diagnosis, especially in children. At time of diagnosis, 55% of children and 27% of adults had anemia and 28% and 16% at one year followup, respectively.

My take: Treatment of the underlying IBD, often helps anemia. However, in some patients treating the anemia with iron may help improve symptoms as much or more than other aspects of treatment.

Related blog post: Microcytic Anemia Review | gutsandgrowth

Sandy Springs, Georgia

Should We Be Excited About a New Medication (Liraglutide) for Obesity?

Posted on July 27, 2015 by gutsandgrowth

Thus far, “the benefits of medications to treat obesity remain limited because of side effects and inadequate efficacy, especially in the long term.” This is part of an editorial (Siraj ES, Williams J. NEJM 2015; 373: 82-3) that explains a recent study (Pi-Sunyer X, et al. NEJM 2015; 373: 11-22). However, there is a huge need for a cost-effective medication because bariatric surgery is not feasible for 400 million obese persons worldwide.

Liraglutide (marketed as Victoza) has been approved by the FDA for weight loss in adults based on this published study and two other trials. Liraglutide is a glucagon-like peptide-1 (GLP-1) mimetic. The authors conducted a 56-week, double-blind trial with 3731 non-diabetic patients. In a 2:1 design, most patients received a once-daily subcutaneous 3.0 mg injection of liraglutide; some received placebo. Both groups received lifestyle counseling.

Key finding:

At week 56, the treatment group had lost a mean of 8.4 kg compared with the placebo group which lost 2.8 kg.

There were similar rates of adverse events (mildly increased in treatment group); the rate of new diagnoses of diabetes was less than one-eighth that in the placebo group. A 2-year extension trial is being analyzed to further pursue this finding. Also, the authors note that 4 cases of breast cancer (0.2%) were detected in the treatment group compared with 1 (0.1%) in the placebo group. This finding could have been due to easier exam following weight loss. It is noted that the labeling for liraglutide has a black box warning regarding thyroid c-cell tumor risk which have occurred in rodents at clinically relevant doses.

A fairly good 2 minute summary: NEJM Short Take on Liraglutide

Despite the weight loss, the editorial has a cautious tone.

“There were statistically significant, although sometimes quantitatively modest, improvements in secondary end points, which included glycemic control, fasting insulin concentrations, cardiometabolic markers, and quality-of-life measures.”
“Most obese participants stayed obese, reversal of the metabolic syndrome was not quantified, and liraglutide may be required indefinitely, like statins, but with delivery by injection and at a nontrivial cost.” According to http://www.goodrx.com, the approximate retail price is $596.01 for 18 mg. For type 2 diabetes, the dosage varies from 1.2 to 1.8 mg per day, after the first week which is dosed at 0.6 mg.

Take-home point: This new medication may help with modest weight loss but at a very significant cost. In addition, long-term data are lacking. Thus, right now, this medication does not provide the cost-effective option to bariatric surgery.

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Georgia Aquarium