Should Teenagers with Severe NAFLD Undergo Bariatric Surgery?

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A recent commentary (Stavra A. Xanthakos and Jeffrey B. Schwimmer. Nat Rev Gastroenterol Hepatol. 2015 Jun; 12(6): 316–318.) discusses the role of bariatric surgery for teenagers with severe nonalcoholic fatty liver disease (NAFLD).  Full text Link: On a knife-edge—weight-loss surgery for NAFLD in adolescents.

Here’s an excerpt:

Abstract: A new position statement from Europe endorses expert-based recommendations to consider bariatric surgery as a treatment for severe NAFLD in severely obese adolescents. This article discusses the problem of severe paediatric obesity, its relationship with NAFLD, and the knowledge and needs regarding bariatric surgery in adolescents… it is critical that adolescents with NAFLD undergoing bariatric surgery be evaluated and managed in bariatric surgery centres with appropriate paediatric multidisciplinary expertise and a commitment to rigorously phenotype NAFLD histology at baseline and to follow outcomes prospectively as long as possible. These procedures can be particularly challenging in adolescents, who are prone to relocate in adulthood and thus might not return for follow-up. High quality prospective multicentre studies with low attrition rates, such as the Teen Longitudinal Assessment of Bariatric Surgery (USA) and the Adolescent Morbid Obesity Study (Sweden) have begun to provide short to intermediate term (1–2 year) outcomes after adolescent bariatric surgery, but do not include prospectively collected data on histological liver outcomes to support evidence-based recommendations regarding NASH as a specific indication for bariatric surgery. However, given the benefits that are emerging for type 2 diabetes and sleep apnoea, (which are comorbid conditions often associated with NASH), we concur with previously published expert guidelines that conclude that bariatric surgery is not contraindicated in a non-cirrhotic patient with NAFLD who otherwise meets appropriate medical and psychosocial criteria for bariatric surgery.2 The adolescent and family should, however, be counselled that a positive outcome with respect to NAFLD is, as yet, not a foregone conclusion.

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Should Patients with IBS be Screened for Celiac Disease?

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Despite widespread expert opinion that those with irritable bowel syndrome (IBS) should be screened for celiac disease, whether it is a good idea is not settled.  A recent study (RS Choung et al. Clin Gastroenterol Hepatol 2015; 13: 1937-43) showed that celiac disease has a low prevalence in US patients (mean age 61 yrs in this cohort) with IBS.

Here’s an excerpt of a summary of this report from the AGA Blog: “Should all Patients with IBS be Screened for Celiac Disease?”

Rok Seon Choung et al investigated whether subjects with positive results from serologic tests for celiac disease are frequently diagnosed with IBS or other functional gastrointestinal disorders (FGIDs).

They sent self-report bowel disease questionnaires to 7217 residents of Olmsted County, Minnesota, to collect data on symptoms compatible with functional GI disorders, including IBS, collecting data on symptoms compatible with functional GI disorders, including IBS. These symptom data were linked to surveys of undiagnosed celiac disease conducted among more than 47,000 individuals from the same region, based on results of tests for immunoglobulin A tissue transglutaminase and then endomysial antibody.

Among the 3202 subjects who completed the questionnaires and had their serum sample analyzed, 13.6% had IBS and 55.2% had some gastrointestinal symptoms.

The prevalence of celiac disease, based on serologic markers, was 1.0%. However, whereas 3% of patients with celiac disease met the criteria for IBS, 14% of patients without celiac disease met the criteria for IBS.

Abdominal pain, constipation, weight loss, and dyspepsia were the most frequent symptoms reported by subjects who tested positive for celiac disease, but none of the gastrointestinal symptoms or disorders were significantly associated with results of serologic test for celiac disease.

My take: This study along with others show that celiac disease is infrequent in patients with IBS.  Since the symptoms of celiac disease overlap with IBS, I doubt this study will dissuade practitioners from screening for celiac despite the low yield.

Also, this fall I posted several blogs on GMOs.  An interesting article (from Vox/Grist) on this subject explains how GMOs are a lot like pornography: It’s practically impossible to define “GMOs”

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Atlanta Sky

Early Study Shows That Relamorelin Impoves Constipation and Transit Time

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An early study shows that Relamorelin relieves constipation & accelerates colonic transit in a placebo-controlled, randomized trial.  Abstract follows.

Relamorelin Relieves Constipation and Accelerates Colonic Transit in a Phase 2, Placebo-Controlled, Randomized Trial A Acosta et. Clin Gastroenterol Hepatol; December 2015Volume 13, Issue 13, Pages 2312–2319.e1. DOI: http://dx.doi.org/10.1016/j.cgh.2015.04.184

Abstract:

Background & Aims

Ghrelin receptors are located in the colon. Relamorelin is a pentapeptide selective agonist of ghrelin receptor 1a with gastric effects, but its effects in the colon are not known. We aimed to evaluate the effects of relamorelin on bowel movements (BMs) and gastrointestinal and colonic transit (CT) in patients with chronic constipation.

Methods

We performed a study of 48 female patients with chronic constipation who fulfilled the Rome III criteria and had 4 or fewer spontaneous BMs (SBMs)/wk. In a randomized (1:1), double-blind, parallel-group, placebo-controlled trial, the effects of relamorelin (100 μg/d, given subcutaneously) were tested during 14 days after a 14-day baseline, single-blind phase in which patients were given placebo at 2 Mayo Clinic sites. The participants’ mean age was 40.6 ± 1.5 y, with a mean body mass index of 25.7 ± 0.6 kg/m2, with 1.7 ± 0.1 SBM/wk, and a mean stool consistency of 1.2 ± 0.1 on the Bristol scale during this baseline period. The effect of treatment on transit was measured in 24 participants with colonic transit of less than 2.4 (geometric center at 24 h) during the baseline period. Gastric emptying, small-bowel transit, and CT were measured during the last 2 days that patients received relamorelin or placebo. Bowel function was determined from daily diaries kept by patients from days 1 through 28. Study end points were time to first BM, SBMs/wk, complete SBMs/wk, stool form, and ease of stool passage. Effects of relamorelin were assessed by analysis of covariance.

Results

Compared with placebo, relamorelin accelerated gastric emptying half-time (P = .027), small-bowel transit (P = .051), and CT at 32 hours (P = .040) and 48 hours (P = .017). Relamorelin increased the number of SBMs (P < .001) and accelerated the time to first BM after the first dose was given (P = .004) compared with placebo, but did not affect stool form. Adverse events associated with relamorelin included increased appetite, fatigue, and headache.

Conclusions

Relamorelin acts in the colon to significantly reduce symptoms of constipation and accelerate CT in patients with chronic constipation, compared with placebo. ClinicalTrial.Gov registration number: NCT01781104.

Lights at Life University

Lights at Life University

More on Staying Up All Night

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In September, this blog (Does Staying Up All Night Affect Surgery the Next Day …) noted a recent study indicating that adverse surgical outcomes with elective daytime procedures were similar irrespective of whether the surgeon had operated overnight.  Some of the letters to the editor on this study were of interest.  In one, the authors note that sleep deprivation was associated with a lower adenomatous polyp detection rate on colonoscopy but was not associated with major complications like death or perforation (M Benson et al. Am J Gastroenterol 2014; 109; 1133-7).  Thus, the letter contends that there are likely to be subtle effects of sleep deprivation on physician performance that could require more sensitive quality metrics.

Another letter notes that extended work was associated with an increased risk of motor vehicle accidents by interns.  The monthly risk increased 16.2% for every extended work shift (LK Barger et al. NEJM 2005; 352: 125-34).  Thus, sleep deprivation could represent a hazard for the physician themselves as well as their patients.

My take: I’m sorry I didn’t quite follow this post. (I was on-call last night.)

Lights at Life University

Lights at Life University

Hepatitis C Cure: Too Late for Many

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Before the recent vast improvements in hepatitis C virus (HCV) treatment, there had been a number of studies predicting a huge increase in HCV-related mortality due to hepatocellular carcinoma (HCC) and cirrhosis.

Despite the optimism that have come with the new treatments, the most recent data (LA Beste, et al. Gastroenterol 2015; 149: 1471-82) continue to predict a huge and increasing burden of chronic liver disease due to HCV.

The authors used a national retrospective cohort of Veteran Affairs (VA) patients with cirrhosis (n=129,998) or HCC (n=21,326) from 2001-13.  They identified an increasing proportion of cirrhosis and HCC during that timeframe.

Key findings:

  • From 2001 to 2013, cirrhosis prevalence nearly doubled (664 –>1058 per 100,000 enrollees) driven by HCV and nonalcoholic fatty liver disease; deaths due to cirrhosis also increased from 83 to 126 per 100,000 patient years
  • From 2001 to 2013, HCC incidence increased 2.5-fold from 17 to 45 per 100,000 patient-years and HCC mortality tripled from 13 to 37 per 100,000 patient-years.  HCC incidence was driven overwhelmingly by HCV.
  • Based on current trends, cirrhosis prevalence will peak in 2021 according to the authors, though they acknowledge that patients from the VA may not be representative of the population at large and that the study has inherent weaknesses due to computerized data collection in this retrospective study.

My take: Despite dramatic improvements in HCV treatment, sadly, it is still going to get a lot worse with regard to disease burden & mortality from HCV before it will improve.

Briefly noted: F Negro. Gastroenterol 2015; 149: 1345-60.  “Extrahepatic morbidity and mortality of chronic hepatitis C”  This review article discusses diabetes, cardiovascular manifestations of HCV, fatigue, cognitive impairment, mixed cryoglobulinemia, and non-hodgkin lymphoma.

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Chattanooga Aquarium

Chattanooga Aquarium

Exome Sequencing in VEO-IBD: More Data

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With more widespread use of whole-exome sequencing (WES), the ability to study the genetic basis for rare disorders like very early onset inflammatory bowel disease (VEO-IBD) has improved considerably. A recent study (JR Kelsen et al. Gastroenterol 2015; 149: 1415-24) analyzed 125 patients (3 weeks to 4 years of age) and compared with pediatric IBD patients (n=45), adult-onset Crohn’s (n=20), and healthy controls (n=145). Link to abstract and online material. (Link includes full-text as well).

The authors focused their study on 400 genes/regions associated with primary immunodeficiency.

Key finding:

  • “Our analysis showed novel and rare variants within these genes that could contribute to the development of VEO-IBD, including rare heterozygous missense variants in IL10RA and previously unidentified variants in MSH5 and CD19.”

In their discussion, the authors elaborate on these findings. In addition, in Table 3, the authors elaborate on potential immunologic studies for these children.

Take home message: The authors recommend “a more complete immunologic evaluation be performed in patients with VEO-IBD.”  Ultimately, understanding the complex genetics will lead to more individualized and successful treatments.

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Lights at Life University

Lights at Life University

Increasing Rates of Professional Burnout

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A recent study (T Shanafelt et al. Mayo Clin Proc. 2015;90(12):1600-1613) indicates that there may be increasing rates of physicians with “Professional Burnout.”  The study is limited by suboptimal response rates but provides some useful information on this topic.

Full text article: Changes in Burnout and Satisfaction With Work-Life Balance in Physicians and the General US Working Population Between 2011 and 2014

Results: Of the 35,922 physicians who received an invitation to participate, 6880 (19.2%) completed surveys. When assessed using the Maslach Burnout Inventory, 54.4% (n=3680) of the physicians reported at least 1 symptom of burnout in 2014 compared with 45.5% (n=3310) in 2011 (P<.001). Satisfaction with work-life balance also declined in physicians between 2011 and 2014 (48.5% vs 40.9%; P<.001). Substantial differences in rates of burnout and satisfaction with work-life balance were observed by specialty.  In contrast to the trends in physicians, minimal changes in burnout or satisfaction with work-life balance were observed between 2011 and 2014 in probability-based samples of working US adults, resulting in an increasing disparity in burnout and satisfaction with work-life balance in physicians relative to the general US working population.  After pooled multivariate analysis adjusting for age, sex, relationship status, and hours worked per week, physicians remained at an increased risk of burnout (odds ratio, 1.97; 95% CI, 1.80-2.16; P<.001) and were less likely to be satisfied with work-life balance (odds ratio, 0.68; 95% CI, 0.62-0.75; P<.001).

The indices that the authors studied included measures of the following (Table 2):

  • Emotional exhaustion
  • Depersonalization
  • Personal Accomplishment
  • Depression: 38% (2011) –>39% (2014)
  • Suicidal ideation: 6.4% (2011) and 6.4% (2014)
  • Burned out rate: 45.5% (2011) –>54.4% (2014)
  • Career satisfaction (would become a doctor again): 70% (2011) –>67% (2014)

Satisfaction with work life balance (Figure 1):

  • Pediatrics generally better than other fields, but close to 50% in 2014 were not satisfied compared with about 40% in 2011 (P <.05).

Take-home message from authors:

Burnout and satisfaction with WLB among US physicians are getting worse. American medicine appears to be at a tipping point with more than half of US physicians experiencing professional burnout. Given the extensive evidence that burnout among physicians has effects on quality of care, patient satisfaction, turnover, and patient safety, these findings have important implications for society at large. 11-20.  There is an urgent need for systematic application of evidence-based interventions addressing the drivers of burnout among physicians. These interventions must address contributing factors in the practice environment rather than focusing exclusively on helping physicians care for themselves and training them to be more resilient.

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Zion National Park

Zion National Park

 

Journals Supplanting Textbooks: Managing Liver Disease

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Between Journals and online resources, textbooks are increasingly less useful.  Case in point -this past month, Clinical Gastroenterology and Hepatology published a special issue: The Art and Science of Managing Liver Disease.  Some of the articles are excellent reviews.

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With autoimmune hepatitis (AIH), the authors make a number of useful points and concisely summarized diagnosis and management.  A few points:

  • Anti-soluble liver antigen/liver-pancreas (SLA/LP) and Asialoglycoprotein receptor (ASGPR) useful in diagnosis of AIH type 1 or 2 and is prognostic for severe disease.
  • In U.S. current guidelines suggest an azathioprine dose of 50 mg (for adults) whereas in Europe the dose is typically 1-2 mg/kg/day.  The authors suggest that the U.S. guidelines could lead to undertreatment, particularly with increasing rates of obesity.
  • The authors state that routine “testing for TPMT deficiency before AZA treatment of AIH is unnecessary, because severe TPMT deficiency occurs in 0.3%-0.5% of the general population and does not invariably cause AZA-induced bone marrow toxicity.” [I will probably continue to check TPMT activity.] They do recommend TPMT testing in cirrhotic patients and those with cytopenias.
  • The authors note that successful long-term withdrawal can occur in 19-40% but recommend biochemical remission (>12-24 months) and histologic remission.  They caution against withdrawal in patients after a relapse due to increased risks of progression to cirrhosis and/or death.
  • When discussing alternative therapies, the authors note that mycophenolate mofetil (MMF) is typically effective for patients intolerant to AZA but not likely to work in AZA nonresponders.
  • Alternative agents reviewed included tacrolimus, cyclosporine, sirolimus/everolimus, rituximab, and infliximab.

Other topics in this issue included NAFLD, HCC, Varices, Hepatic encephalpathy, HBV, HCV, Acute-on-Chronic Liver Failure, PSC and Malignancy, DILI, and noninvasive imaging for liver fibrosis.

Tipping Point for Obesity?

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A bit of encouraging news from California where investigators showed a small drop in the prevalence of childhood obesity from 2008 to 2013 (C Koebnick et al. J Pediatr 2015; 167: 1264-71).  Using a population-based cohort of ~1.3 million patients, the authors found the following:

  • Obesity prevalence decreased from 19.1% (2008) to 17.5% (2013).  This was observed across all ages, sexes, races, and socioeconomic groups but with variability.
  • Younger children had a greater decline in obesity prevalence compared with adolescents: ages 2-5 years:  -15.4% decline, ages 6-11 years: -11,8% decline and in 12-19 years: -4.5%.

My take: This is a good indication that increased awareness of the obesity epidemic may be leading to some improvement.

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Lights at Life University

Lights at Life University

Hypothyroidism with ATP8B1 Deficiency

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A recent study (L Li et al. J Pediatr 2015; 157: 1334-9) indicated that hypothyroidism may be another extrahepatic feature of patients with ATP8B1 deficiency; this mutation’s main manifestation has been intrahepatic cholestasis in either progressive familial intrahepatic cholestasis (PFIC type 1) or benign recurrent intrahepatic cholestasis (BRIC type 1).

In this study, 3/13 were hypothyroid and an additional 2/13 had subclinical hypothyroidism.  These patients were compared with a cohort of children with ABCB11 deficiency (PFIC type 2 or BRIC type 2) in which 0/19 had hypothyroidism.

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