HCV now more deadly than HIV

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Hepatitis C virus (HCV) now kills more people in the United States than HIV (Ann Intern Med 2012; 156: 271-78).  Data from the CDC followed the mortality burden of Hepatitis B (HBV), HCV, and HIV from 1999 to 2007.    The data were derived from death certificates & a limitation was that these are often completed by individuals other than the primary physician.  Sometimes the exact cause is difficult to discern.  However, this is more likely to result in underreports of deaths from viral hepatitis compared with those from HIV.

In total, 21.8 million death certificates were analyzed.

  • HBV death rate stayed relatively constant –in 2007: 1815 deaths*
  • HCV death rate increased steadily –in 2007: 15106 deaths*
  • HIV death rate improved –in 2007: 12734 deaths*

*When infection was cause or underlying contributor of death

One in 33 baby boomers are infected with HCV; most do not know they are infected.  Three-fourths of the deaths for HCV are in this age group as well.  In addition, it is expected that mortality from HCV will grow over the next 10-15 years without a major intervention. http://www.ajc.com/health/hepatitis-c-deaths-up-1356460.html

Given the increasing HCV disease burden, this strengthens the rationale for more aggressive case finding and the use of more effective & more expensive therapies (see previous blog: The cost of progress in treating Hepatitis C.  Among patients with HCV with advanced disease/cirrhosis, monitoring for HCC is important (Looking for trouble).

Additional references:

  • -Hepatology 2011; 54: 1547. Excess mortality (6x gen population) in those who achieve SVR
  • -Gastroenterology 2010; 138: 513. Predicts peak cirrhosis due to HCV in year 2020; peak HCV prevalence was year 2000.
  • -Clin Gastro Hep 2010; 8: 924. Epidemiology 2010.
  • -Hepatology 2010; 52: 1543. Visceral adiposity is associated with increased histological findings and higher viral loads.
  • -Gastroenterology 2010; 138: 136. Predicting clinical outcomes: plt<99, Alb <3.5, AST/ALT ratio >1.2, & TB>2 all assoc with 40-50% risk of developing ‘clinical outcome’ in next 3.5yrs. Outcomes: ascites, variceal hemorrhage, decompensation according to CTP (66%), peritonitis, death (2%), encephalopathy
  • -Hepatology 2009; 49: 729. 5-yr f/u after successful HCV RX, n=150. 2 developed HCC.
  • -Gastroenterology 2009; 136: 138, 39(ed). HCC occurring c HCV ~1%/yr in HALT-C study. prolonged Rx -not helpful. n=1005
  • -Hepatology 2008; 47: 1128. Increasing mortality of HCV between 1995-2004. Due to aging of infected individuals.
  • -Hepatology 2008; 47: 1371. Genotype 4 review.
  • -Hepatology 2008; 47: 836. 2/121 bx of children had cirrhosis.
  • -J Pediatr 2007; 150: 168. n=60. Looked at two populations: look back after transfusion and referrals. mean age at infection 7 months, mean time with infection 13yrs. 12% developed significant fibrosis.
  • -Hepatology 2007; 45: 1076. Large study: Lancet 2006; 368: 938. 39,109 c HBV, 75,834 c HCV, 2,604 c both. death rate: 3.2%, 5.3%, 7.1% respecively. Increased rate of dying c HCV due to drug use rather than liver dz.
  • -Clin Gastro & Hep 2006; 4: 1190-1191, 1271-78, 1278-1282. slow progression of HCV in 184 untreated women infected in 1977 (mean 27 years) — 2.1% developed cirrhosis. genotype 1B ALT values correlated with change in histology.
  • -JPGN 2006; 43: 209. Review of 91 cases; 7 c cirrhosis at presentation (mean 11.7yrs)
  • -Clin Gastro & Hep 2005; 3: 910. cirrhosis in 71% after 60 years in Asian patients; 25% in Caucasian pts 61-80 who presumably had disease for shorter interval.
  • -Gastroenterology 2003; 125: 1695. obesity/insulin resistance worsens fibrosis in HCV
  • -Gastroenterology 2002; 123: 483-491. IFN Rx improved survival; n=2889. retrospective study.
  • -JPGN 2001;33: 22A. spontaneous clearance in 30% during short f/u; n=145.
  • -Hepatology 2000; 32: 91-96. Low likelihood of progression in cohort followed for 20yrs.

More bad news for smokers

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Add two more cancer risks for tobacco smoke (Gastroenterology 2012: 142: 233-40, 242-47).  There is now evidence linking tobacco smoke to 18 different cancers and tobacco smoke is probably the most preventable cause of death in the world.

In the first study, the investigators examined 3167 patients with Barrett’s esophagus.  This retrospective study followed patients for 7.5 years.  Patients who were current smokers (any form of tobacco) had double the risk of developing high-grade dysplasia or cancer compared to those who had never smoked.  Former cigarette smokers had a hazard ratio of 1.53.

In the second study, 386 patients with Lynch syndrome were analyzed during a 10 month period.  The hazard ratio for developing colorectal adenomas was 6.13 for current smokers and 3.03 for former smokers compared with patients who never smoked.  In addition, the authors identified a trend for developing adenomas based on pack-years.

Two more reasons to quit smoking.  On a side note, my grandmother said quitting smoking was the easiest thing that she ever did.  So easy, she did it a thousand times.

Additional references:

  • -Gastroenterolgy 2005; 129: 1825-31.  1.6% incidence of BE in adult Swedish population. Alcohol & smoking increase risk.
  • -NEJM 2011; 365: 1222. Treating smokers -useful review.
  • -NEJM 2011; 365: 1193. Cytisine -inexpensive- helps with smoking cessation (8.4% success vs 2.4%in placebo)
  • -NEJM 2008 358; 2249. Smoking and role of social networks.
  • -Gastroenterology 2011; 141: 2000. Lower risk of Barrett’s in pts taking NSAIDs & statins. n=570.
  • -Gastroenterology 2011; 141: 1179. Lower risk of Barrett’s in pts with low-grade dysplasia than previously noted -similar to non-dysplastic Barrett’s.
  • -NEJM 2011; 365: 1375. Large Danish study, n=11028. Lower incidence of Barrett’s than previous estimates. Relative risk of 11.3 compared to general population for adenoca of Esophagus with absolute annual risk of 0.12%. Barrett’s patients have the same life expectancy as general population (ed. pg 1437). Detecting cancer only ~1 in 1460 scopes with screening whereas Barrett’s detected in 10% of pts.
  • -Gastroenterology 2011; 140: 1084. AGA statement on Barrett’s . Recs screening only in those with multiple risk factors (age 50, male, chronic GERD, white, incr BMI)
  • -NEJM 2005; 352: 1851. Cases of Lynch can be missed when following screening guidelines.
  • -Gastroenterology 2010; 138: 207-2177 (entire issue) Colon cancer, Lynch syndrome
  • -Gastroenterology 2008; 135: 380.  Review of colon cancer screening and prevention -2008 up-to-date- literature review
  • -Gastroenterology 1967; 53: 517-27.  Seminal article.  Lynch HT showed gene-related cancer in family cancer syndrome -different than polyposis syndromes.

Sarcopenia, fatigue, and nutrition in chronic liver disease

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Several articles from a recent Clinical Gastroenterology and Hepatology have addressed nutritional aspects of chronic liver disease.

1. Sarcopenia?  This term refers to generalized loss of skeletal muscle.  It does not equate to malnutrition though there is significant overlap.  (Clinical Gastroenterology and Hepatology 2012; 10: 166-73 & editorial 100).  In this study, 112 adults with cirrhosis had CT scans which examined skeletal muscle at the L3 level; 40% had sarcopenia. Sarcopenia was independently associated with mortality and was not reflected in MELD score.  Patients had increased risk of death from sepsis and liver failure (HR 2.18).  Thus, sarcopenia joins hyponatremia, refractory ascites, hepatic encephalopathy as additional factors which add prognostic information to MELD score.

2. Fatigue in cirrhosis. (Clinical Gastroenterology and Hepatology 2012; 10: 174-81 & editorial 103).  Fatigue is common in cirrhosis and is multifactorial.  In this prospective study, 108 patients were evaluated with a fatigue impact scale. Fatigue improved after liver transplantation. Fatigue can be peripheral due to muscle weakness and dysfunction. And, fatigue can be central due to difficulty performing physical and mental activities.  Central fatigue is associated with an increased perceived effort for tasks and often related to depression; this type of fatigue is much more common with cirrhosis.  Although improved, fatigue often does not completely resolve with liver transplantation.

3. Nutrition recommendations. (Clinical Gastroenterology and Hepatology 2012; 10: 117-25).  A summary of nutrition recommendations in adults  with chronic liver disease is given in this article.  One common misconception is protein restriction.  This is not beneficial.  Protein recommendations are for adult patients with cirrhosis to receive 1-1.5 g/kg/day.  This amount is higher than for healthy individuals.  Protein restriction leads to protein catabolism, muscle breakdown and increases the likelihood of hepatic encephalopathy.

Additional references:

  • -Age Ageing 2010; 39: 412-23.  Sarcopenia consensus definitions in older people.
  • -Gastroenterology 2008; 134: 1741. Evaluation and management of end-stage liver disease in children. Recs vaccines due to functional asplenia/portal hypertension at age 2 for Neisseria (MCV4) or polysaccharide (MPSV4); at 6 weeks of age for pneumococcal conjugate vaccines. Reviews nutrition, varices, ascites, encephalopathy….
  • -Liver Transplant 2008; 14: 585-591. Poor growth often due to growth hormone resistance. Chronic malnutrition is a factor, but children with advanced liver dz may not grow despite adequate calories. Recs: for chronic liver dz: 130-150% of RDA based on ideal body wt; in infants 120-150 cal/kg/day. Increase MCT either thru formula or supplemental MCT.
  • -Liver Transplant 2006; 12: 1310. Review article on nutrition for OLTx patient.
  • -JPGN 2000; 30: 361. nutrition review and chronic liver disease.

Methotrexate and liver toxicity

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There are drawbacks with all of the therapies for inflammatory bowel disease; however, usually the inflammatory bowel disease is worse than any of the medications. One of the therapies that  has started to see increased usage in Crohn’s disease is methotrexate (MTX), both as an alternative to thiopurines and as an adjunct to Remicade.  There are a number of side effects; a patient handout is available at the following: http://www.ccdhc.org/diseases/MethotrexateLetter.pdf

One of the concerns with MTX has been liver toxicity, in part because of descriptions in the rheumatology literature with long-term usage.  In Crohn’s disease patients, it appears that the risk is much lower (Inflamm Bowel Dis 2012; 18: 359-67).  This study found 13 trials for their meta-analysis.  A total of 632 participants were included: 373 MTX, 131 thiopurines, 128 placebo.  In the MTX group, elevated hepatic aminotransferases occurred in 1.4 per 100 person-months.  The rate of elevation more than 2-fold the upper limit of normal was 0.9 per 100 person-months.  Thus, of the initial 373 patients, 39 had an abnormal aminotransferase.  26 of these 39 had spontaneous resolution, 3 improved with dose reduction & 10 withdrew from MTX treatment (0.8 per 100 person-months).  Seven of these withdrawals were from one of the earlier studies (Feagan et al. NEJM 1995; 332: 292-97). Besides the low likelihood of needing to stop MTX due to liver toxicity, the other observation was that the liver toxicity was mostly dependent on the dose; therefore, dosage reduction would likely be effective if needed.

In my practice, when considering MTX treatment, I usually recommend the following:

  • Monitoring: Baseline: CXR, CBC, Amylase, Renal, LFTs, urine HCG & then Q2-4 weeks initially, then Q3months
  • Give Folate during therapy.
  • Use zofran if needed for nausea
  • Avoid NSAIDs during treatment due to renal toxicity
  • Contraindicated with pregnancy (MTX=teratogen) -females should see gynecology
  • Families warned in writing that this medication is given once a week; more often can be deadly

Additional references:

  • -IBD 2011; 17: 2521. ~25% remission at 1yr, 16% at 2yrs.. n=93.
  • -JPGN 2011;53: 389. n=64. Supports use of zofran for 1st few months to prevent nausea.
  • -JPGN 2010; 51: 714. Use of MTX after thiopurines. n=27. 48% in remission at 6 months.
  • -JPGN 2009; 48: 526. Use in pediatric CD, n=25. 64% response
  • -JPGN 2009; 48 suppl 2: S111. MTX may be effective for UC.
  • -NEJM 2008; 359: 2790. Similar safety of AZA and MTX in vasculitis patients. AZA may be safer.
  • -IBD 2008; 14: 756. MTX in Crohn’s. n=39. 71% remission (20% steroid-free).
  • -J Clin Pharm & Therapeutics 2007; 32: 327-31.
  • -Am J Health Syst Pharm 2004; 61: 1380-84. review of MTX errors -FDA reported
  • http://www.npsa.nhs.uk/patientsafety/alerrts-and-directives/alerts/oral-methotrexate/
  • -Am J Gastro 2007; 102: 2804-2812. n=60 pediatric patients. ~42% in remission with MTX & ~50% improved. 13% (8) had to stop due to increased LFTs or sepsis.
  • -IBD 2006; 12: 1053. n=61. MTX for AZA nonresponders/breakthroughs: 80% with improvement/ 45% with long-term response; 10% discontinued due to side effects. Steroids stopped in 36.
  • -JPGN 2005; 40: 445. Oral MTX works as well as IM/SC.
  • -JPGN 2003; 37: 392 (194A) 0.4 mg/kg/weekly. 91% response at 2 mo, most still needed remicade
  • -Gastroenterology 2003; 124: suppl 1, A-41 (305) 11/12 responded – able to stop remicade
  • -Feagan et al. NEJM 1995; 332: 292-97.
  • -J Pediatr 1999: 134: 47. Hepatotoxic risk factors. (enzymes & obesity). Consider bx if serial enzymes increased >40% of the time over 1 year
  • -Arthritis Rheum 1997; 40: 2226.

More imaging needed?

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With new tools at our disposal in diagnosing inflammatory bowel disease, we need to decide how and when to use them.  Potential new modalities include stool inflammatory markers, video capsule endoscopy, CT enterography (CTE), and MR enterography (MRE).  Several studies have shown that the information that these studies yield may change management. The latest of these studies (Inflamm Bowel Dis 2012; 18: 219-25) looked at how the knowledge of CTE effected management and physician confidence with Crohn’s disease.

The authors prospectively assessed 273 patients with established or suspected Crohn’s disease.  In their analysis, 70 patients (48%) of established cases had altered management because of CTE and 69 (54%) of suspected cases.  These changes were considered to be  independent of clinical, serological or histologic findings.  Changes included medication modification in 45 (16.2%), excluding Crohn’s disease in 46 (16.8%), surgery referral in 10 (3.7%), alternate diagnosis established in 9 (3.2%), & canceling surgery in 7 (2.6%).  The authors considered excluding active small disease as an important management plan change; this occurred in 18 patients (6.6%).

The authors state that their current practice is to use MRE for serial imaging rather than CTE, to minimize risks from radiation; though CTE is often the initial imaging.

My take on this article is that information from imaging often increases the certainty about the diagnosis and gives a more complete picture of the severity.  It is likely that more information leads to more aggressive therapy.  At the same time, in pediatric gastroenterology, the trend towards using more effective therapy earlier in the course of the disease has developed even in the absence of extensive imaging (see previous: Only one chance to make first impression).  Whether more imaging in pediatric patients would be worthwhile is not known.

Additional references:

  • -JPGN 2008; 47: 31.  Capsule endoscopy may reclassify pediatric IBD
  • -NEJM 2010; 363: 1, 4. Safety of CT. Can have overdose of radiation and even standard doses could cause complications. Also, a big issue is downstream unnecessary testing due to incidental findings.
  • -Clin Gastro 2008; 6:283. Use of CT enterography.
  • -JPGN 2010; 51: 603.  MRE for suspected IBD.  Useful in Crohn’s disease.
  • -IBD 2004;10: 278-285.  WCE for Crohn’s (review)  Capsule can help differentiate UC from Crohn’s.

What to make of FODMAPs

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Consumption of FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) may trigger irritable bowel syndrome (IBS) symptoms.  Some research indicates that a diet low on FODMAPs may be beneficial (J Hum Nutr Diet 2011; 24: 487-95).  This study tried to assess whether a low FODMAPs diet which had been reported from a single center in Australia would be effective for IBS.

In this study, consecutive patients with IBS were divided into two groups.  39 received standard dietary advice based on UK National Institute for Health and Clinical Excellence (NICE) guidelines.  43 patients were placed on a low FODMAP dietary advice.  Patients were selected into each group consecutively (not randomized). This study reported a 76% satisfactory symptom response in the FODMAP group vs a 54% response in the control group (p=0.038).  Overall, 86% of FODMAP group had improved composite score compared with 49% of standard treatment group. Specific improvements were noted in bloating, abdominal pain, and flatulence.  The average age of the study population was 38 and 71% were females.  60% had diarrhea-predominant IBS.

NICE guidelines for IBS:

  • Healthy eating principles: regular eating, taking time to eat
  • Limit high fat foods and fizzy drinks
  • Limit insoluble fiber for diarrhea and gradually increase for constipation
  • Limit sugar-free sweets and foods with sorbitol
  • Limit fruit to 3 portions/day
  • Avoiding ‘resistant’ starch may be useful (eg. sweetcorn, green bananas, part-baked and reheated bread)
  • Addition of oats and linseeds may be helpful

Low FODMAP diet

  • Reduce high fructan foods (eg wheat and onion)
  • Reduction in high galactooligosaccharide foods (eg chickpeas, lentils)
  • Reduce high polyol foods and polyol-sweetened sources.  Replace with suitable fruits and vegetables
  • In patients with lactose malabsorption, reduce high lactose foods (eg milk, yoghurt) to smaller volumes or substitute lactose-free products
  • In those with fructose malabsorption, decrease excess fructose

Of course, reading the author’s description of a low FODMAP diet is confusing.  Translation:

Include more bananas, blueberries, lettuce, potatoes, gluten-free breads or cereals, rice, oats, hard cheeses, lactose-free milk, sugar, molasses, and artificial sweeteners that do not end in “ol.”

Avoid/eliminate apples, pears, canned fruits in natural juices, high-fructose corn syrup, cows’ milk (due to lactose), soft cheese, broccoli, cabbage, pasta, bread, baked goods from wheat/rye, mushrooms, and sweeteners like sorbitol or others that end in “ol.”

Since this diet has attracted more widespread attention, basic familiarity is important for all physicians who treat IBS.  A useful resource to explain this diet is the Wall Street Journal:

http://online.wsj.com/article/SB10001424052970204554204577023880581820726.html

This link has a good table illustrating the recommended dietary choices.

Whether FODMAPs will be superior to other dietary advice for IBS is still uncertain.  Though, given the limited number of effective treatments for IBS, this small study is a promising development.

Additional references:

  • -Clin Gastro & Hep 2009; 7: 706. n=17. 13 responded to very low carb diet (<20g/day)
  • -Clin Gastro & Hep 2008; 6: 765. Dietary triggers for IBS include fructose/fructans: honey, high fructose corn syrup, wheat, fruits.
  • -IBD 2006; 13: 91. Dietary guidelines for IBS.
  • -Clin Gastro Hepatol 2005; 10: 992-996. Obesity increases IBS symptoms; diet with low fat, high fruit/fiber have fewer symptoms
  • -Gut 2004; 53: 1459-1464. Food elimination based on IgG antibodies. Patients did better on diet with implicated foods than with control diet (diet was blinded/randomized).
  • -Am J Gastro 2011; 106: 508-514. randomized, double-blind trial showing efficacy of GFD for non-celiacs.  60% vs 32& placebo response.
  • -Nutr Clin Pract. 2011;26:294-299.  GFD for non-celiacs.
  • -Gastroenterology 2011; 141: 1941./Am J Gastro 2011; 106: 915.  Exercise improves IBS symptoms.

Big gift, how much risk

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When an individual is considering donating a part of their liver, it is no exaggeration to say this may be lifesaving.  In pediatric hepatology, live donor liver transplantation (LDLT) is frequently considered by desperate parents. The risk of this gift has been poorly understood due to a lack of a LDLT registry.

This month (Gastroenterology 2012; 142: 273-80) better data has emerged.  By combining information from UNOS and the Social Security Death Master File, the authors were able to follow 4111 LDLTs (donors) in the U.S. between 1994 and 2011. Key findings:

  • Seven early deaths (1.7 per 1000)
  • Death rate was not affected by portion of liver donated
  • 11 early catastrophic events: early deaths or acute liver failure (2.9 per 1000)
  • Long term mortality was similar to that for live kidney donors and NHANES III healthy participants over 11 year followup (1.2%, 1.2%, and 1.4% respectively)

Although these data are somewhat reassuring, there is a definite increase in mortality and morbidity among LDLT donors.  An editorial in the same issue (pg 207-09) states that LDLT donors are probably healthier than the general population; up to 65% of donor candidates are rejected during the evaluation process.  As such, when survival at 11 years is similar to NHANES III participants, this indicates the likelihood of a detrimental effect on long-term health. Besides early perioperative deaths, suicide and drug overdoses among donors was significant (n=4) and 4% of donors may develop psychiatric problems.  Specific complications include biliary leaks (9%), bacterial infections (12%), and incisional hernias (6%).

At the same time, the direct benefit of this gift including the potential of saving a loved one cannot be measured.  In addition to avoid a protracted uncertain period on the waiting list for a recipient, a donated liver may help another unidentified individual obtain a deceased donated liver.

Additional references:

-Gastroenterology 2008; 135: 468. Donor morbidity/mortality. n=393. 62% without complications. 3 deaths and significant morbidity.
-Liver Transplantation 2006; 12: 499. Review.
-DDW 2003, T Tran, n=56. only 27% of prospective donors c nl histology.
-NEJM 2003; 348: 818-25. (L & R-Lobe) complications from donating in 449. 6% biliary complications, reop in 4.5%, death 0.2%
-NEJM 2002; 346: 1074-1082. & 1038. R lobe Tx.
-J Pediatr 1999; 134: 280.  Results of LDLT: 92% 1 yr survival; higher biliary complications 19-34%.

Holes in the fiber theory

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Since the 1970s, it has been accepted that diverticular disease is related to low fiber intake and the Western diet.  Problem is that this might not be right (Gastroenterology 2012; 142: 205-10).  In this observational cross-sectional study (n=2104), low dietary fiber was not associated with diverticulosis; just the opposite.  High fiber intake, after adjusting for other factors, had an adjusted prevalence ratio of 1.3.  Due to the nature of the study, there may be potential bias that would not be present with a prospective study, especially with regard to dietary recall.  An editorial in the same issue (pg 205-07) lists three other studies; two of these also could not demonstrate a protective effect of fiber.  In addition to these findings, this study did not find an association between fat, red meat, physical activity and diverticulosis.

Although these data throw a big question mark regarding the pathogenesis of diverticular disease, this does not mean you should throw away your fiber bars quite yet.  Although low fiber may not cause diverticular disease, several large prospective studies have been completed which convincing show an association with lower complications/hospitalizations among individuals with higher fiber intake.  In addition, increased fiber in the diet has been shown to lower cardiovascular complications.

Additional references:

  • -Br Med J 1971; 2: 450-54.  Seminal article on diverticular disease and association with Western countries with low fiber intake.
  • -Am J Clin Nutr 1994; 60: 757-64.  Prospective study showing benefits of fiber in preventing diverticular complications (n=47,888); RR=0.58 for developing symptomatic diverticulitis.
  • -BMJ 2011; 343: d4131.  EPIC study, n=47,033, showing benefit of fiber in reducing hospitalizations due to diverticular dz over 12yrs (0.59 RR)
  • -NEJM 1999; 340: 169. fiber does not decrease Colon Ca risk.
  • -NEJM 2000; 342: 1149 & 1159. fiber does not decrease risk of recurrent adenomas.
  • -Am J Clin Nutr 2000; 70: 1433-1438. Fiber lowers cholesterol & can decrease risk of heart attack by 15%.

Food as medicine

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Two recent articles add some useful information regarding enteral therapy for Crohn’s disease (Inflamm Bowel Dis 2012; 18: 246-53 & JPGN 2012; 54: 298-305).

The first article enrolled 34 children with newly-diagnosed Crohn’s disease.  Patients were divided into elemental and polymeric formula groups and followed in a prospective, double-blind randomized controlled trial for two years.  Measures of improvement included the PCDAI as well as fecal calprotectin and fatty acids.  Both groups of patients responded clinically.  93% (14/15) of the elemental formula group achieved remission based on PCDAI scores (<11) and 79% (15/19) of the polymeric formula group.  The initial treatment was use of formula (along with only clears) either by NG or oral for 6 weeks.  All patients had NG placed at time of endoscopy and if sufficient oral intake was demonstrated (for 2 days), NG was removed.  All subjects had small bowel and colonic disease.  Although calprotectin levels decreased, they remained very elevated.  In the EF group, the median calprotectin dropped from 2023 μ/g to 1113 μ/g, though only one patient had a level below 400; similarly in the PF group the calprotectin dropped from 1929 μ/g to 1134 μ/g, and only two patients had a level below 400.  Some to the reasons why changes in diet may be useful have been alluded to in a previous post: Eat your veggies…if you don’t want to get sick.

The second reference is a clinical guideline on the use of exclusive enteral nutrition EEN).  The introduction notes that 65% of European pediatric gastroenterologists use EEN compared to 4% for North American pediatric gastroenterologists.  In pediatric trials, EEN and corticosteroids were considered ‘equally effective’ in a pediatric meta-analysis which included five randomized controlled trials (n=147).  However, a Cochrane review favored corticosteroid treatment over EEN in a meta-analysis that included adult and pediatric patients (n=192 EEN, n=160 corticosteroids).  According to the authors, small studies have demonstrated other potential advantages of EEN including higher rates of mucosal healing and better linear growth.  With regard to mucosal healing, the initial cited study casts with ongoing elevated calprotectin indicates that this does not occur in the majority of children with EEN therapy.  Other caveats:

  • Disease location: some evidence favors small bowel disease rather than colonic disease
  • Formula composition: does not seem to matter whether elemental or polymeric
  • Duration of therapy: majority treat for 6-8 weeks of EEN.  The authors recommend at least 8 weeks
  • Time for response: Inflammatory markers improve in a little as a week, remission typically 2-4 weeks
  • Concomitant medications: many places initiate immunomodulator treatment; others cycle EEN
  • Start with goal 120% of ‘maintenance’ nutrient needs.  On 1st day, authors recommend starting at 1/2 goal volume and gradually increase over 1-2 days
  • Partial enteral nutrition (PEN) (eg. overnight feedings & normal daytime diet) has been helpful in improving growth and may improve remission rates.
Why not EEN or PEN? Potential barriers include cost, difficulty changing diet, fear of tube feedings, and more acceptable alternatives.  At the same time, some of these barriers could be overcome.  Quality of life measures have improved in children receiving enteral nutrition.

The use of more top-down therapy may affect all of the above considerations (Only one chance to make first impression).

Additional references:

  • -Cochrane Database Syst Rev 2007; CD000542.  Enteral nutritional therapy vs corticosteroids to induce remission in Crohn’s disease.
  • -Gastroenterology 2011; 141: 742. AGA guidelines on use of enteral nutrition in wide variety of conditions.
  • -Gastroenterology 2008; 135 : 1005. omega-3 fatty acids ineffective in Crohn’s dz for maintaining remission.
  • -Pediatr Res 2007; 61: 356-60.  Enteral nutrition effect on protein turnover in adolescents with Crohn’s disease.
  • -J Pediatr 2000; 136: 285-91. Nutritional Rx w polymeric diet is effective w/in 8 weeks in 32/37.
  • -Scand J Gastro 2001; 36: 383-8. Elemental & polymeric diets successful in maintaining remission in ~43% of adults with complete steroid withdrawal
  • -JPEN 1992; 16: 499. improved wt,ht, decreased prednisone, decreased CDAI
  • -JPGN 2000; 31 (supp 2) A291. Polymeric vs elemental diet.
  • -JPGN 2002; 35: 339-40. Lactase deficiency – same prevalence in IBD as in RAP.
  • -JPGN 2000; 31: 3 & 8. EN about as effective as steroids for primary Rx.

Pain changes brain

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For several years, there has been research showing changes in PET scans and functional MRI in association with functional abdominal pain.  A recent article goes a step further showing microstructure  brain changes in patients with chronic pancreatitis (Gut 2011; 60: 1554-62).

This study examined 23 patients with pain due to chronic pancreatitis and 14 controls.  Using a 3T MR scanner, apparent diffusion coefficients (ADC) and ‘fractional anistotropy’ (FA) values were assessed in numerous parts throughout the brain.  This new technology, uses an MRI for diffusion tensor imaging which assesses changes in white and grey matter microstructure not evident with more conventional imaging.  Chronic pancreatitis patients had increased ADC in the amygdala, cingulate cortex, and prefrontal cortex.  In addition, FA values were reduced in the cingulate cortex and secondary sensory cortex.  These areas of the brain with these changes are known to be involved in the processing of visceral pain.  Microstructural changes were correlated to patients’ clinical pain scores.  Some of the changes can be influenced by other factors including alcohol usage, depression, Alzheimer’s or diabetes.

This study echoes findings from others that demonstrate structural reorganization of the brain in association with chronic pain.

Additional references:

  • -Gastroenterology 2010; 139: 1310. n=15 IBS women, 12 controls.  IBS pts have emotional modulation of neural responses to visceral stimuli (eg rectal stimulation) –based on functional MRI studies.
  • -Gastroenterology 2006; 130: 26 & 34. Functional MRI measured in response to barostat show increased sensitivity in pts c IBS. Also, altered 5-HT signaling in IBS-D & IBS-C.
  • -J Pediatr 2001; 139: 838-843. Pts c IBS, RAP more sensitive to visceral perception in rectum and stomach respectively.
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