Colonic disease and PSC

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While primary sclerosing cholangitis (PSC) has been associated with inflammatory bowel disease, and ulcerative colitis (UC) in particular, the pathogenesis of this relationship has not been established.  A fascinating observation on this relationship is that an inflamed colon is important in PSC development (Clin Gastroenterol Hepatol 2012; 10: 439-41).

In this study which reviewed 2754 Irish patients with IBD, 59 (2.2%) had PSC.  PSC incidence correlated with increasing colonic involvement.  Among the 13 patients with Crohn’s disease, none had isolated small bowel disease.  The second part of the study involved a review of 82 separate PSC patients attending the Irish National liver transplant unit.  The majority of ulcerative colitis patients had a pancolitis; all 10 PSC patients with Crohn’s disease had colonic involvement.

Since PSC occurs without IBD, colonic inflammation is not necessary for PSC development.  However, in patients with IBD, colonic inflammation is very important.  In fact, in a previous study of 53 PSC-IBD patients, no UC patient status post a colectomy had recurrent liver disease following liver transplantation whereas seven patients with intact colons had recurrent disease following liver transplantation.

The authors speculate that bacterial translocation along with subsequent portal bacteremia may be an important step in pathogenesis among these patients.

Additional references/previous posts:

Salmonella by mail-order

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Sometimes patients are amazed that hemoccult cards can be sent by mail.  Now, I learned something new: you can mail-order live poultry and thereby spread salmonella far and wide (NEJM 2012; 366: 2065-73).  This study identified 316 cases in 43 states.

Key findings:

  • 36 hospitalized (23%)
  • 38 had chicks as pets (42%); of these, 22 (69%) said the pet owner was a child <5 years
  • Salmonella enterica serotype Montevideo subtype
  • 81% of infections identified as coming from a hatchery in Western U.S.
  • After identification of problem, owners implemented recommendations which lowered salmonella contamination.  After these measures, outbreak strain still detected in 7% of samples
  • Hatcheries mail live poultry to all 50 states –4 million birds are produced annually for this purpose. Approximately 250,000 birds are shipped each week, usually within 24 hours of hatching; each costing about $5 each.

Because only a portion of salmonella infections are identified with laboratory tests, there are likely thousands more infections associated with this outbreak.  Overall, nontyphoidal salmonella infections are estimated to cause 1 million illnesses, 19,000 hospitalizations, and 370 deaths annually.  Most infections are acquired as foodborne illnesses.  Though contact with animals, as this report indicates, is another mechanism.  These birds can appear healthy and intermittently shed salmonella.

Individuals wishing to reduce their risk of illness should practice careful hand hygiene around animals.  See link for helpful advice:

http://www.cdc.gov/healthypets/resources/salmonella-baby-poultry.pdf

The poultry business can help by adhering to sanitary practices, by avoiding artificially coloring chicks (which targets children), and by warning recipients of the danger of salmonella infection.

More on perinatal HBV

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In addition to a recent blog entry (How to stop HBV vertical transmission), several other recent articles add information about HBV vertical transmission:

  • Gastroenterology 2012; 142: 773-81.  Data from 2386 Taiwanese children born to HBsAg-positive mothers were examined.  HBeAg-positivity increased the likelihood of having an HBV-infected infant (9.26%) despite appropriate immunization & HBIG.  Since HBeAg-posiitivity is associated with higher HBV DNA levels, this is logical based on previous studies. Fulminant HBV developed in 1 of 1050 children who did not receive HBIG; in this study, the majority of mothers with HBeAg-negative HBV did not receive HBIG.
  • Pediatrics 2012; 129: 609-16.  This study examined HBV prevention in the U.S. from 1994-2008.  The CDC created the US Perinatal Hepatitis B Prevention Program (PHBPP) to accelerate progress at eliminating perinatal HBV transmission.  While the number of infants born to HBsAg-positive women with HBV increased from 19,208 to 25,600, the incidence of infants with chronic hepatitis B virus infection among tested infants decreased from 2.1% in 1999 to 0.8% in 2008.  This is due to the fact that 94.4% of PHBPP-managed infants received HBV vaccine and HBIG within 1 day of birth.  Yet, gaps remain.  The number of infants who completed the vaccine series by 12 months actually declined from 86% (1994) to 77.7% (2008). And, in 2008 only one-quarter of CDC’s 25,6000 infants born to HBsAg-positive women had known serologic outcomes.

Related previous post: Looking for trouble

Food choices, FODMAPs, and gluten haters

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Given the frequency of functional gastrointestinal diseases (FGID), including irritable bowel syndrome (IBS), dietary treatments that may improve symptoms receive a lot of attention.  A recent review of the role of food choices in the development and management of FGIDs is a useful reference (Am J Gastroenterol 2012; 107: 657-66 -thanks to Ben Gold for forwarding this article).

This review details specific dietary advice as well as the following specific physiologic effects of FODMAPs:

  • Osmotic effects
  • Bacterial fermentation
  • Motility effects
  • Prebiotic effects
  • Systemic effects –mild depression, tiredness
In addition, the review looks at other potential foods which could serve as a trigger for IBS symptoms, like gluten & summarizes why some IBS patients are gluten haters.  The authors acknowledge that gluten sensitivity, in the absence of celiac disease, does not have a known mechanism.  Until a reliable marker becomes available, the importance of gluten sensitivity for FGIDs is unknown.
Related posts:

What to make of FODMAPs

Gluten sensitivity without celiac disease

Is a biopsy necessary in Celiac disease?

Alive and well? 10 years after liver transplantation

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As survival has improved with liver transplantation (LT), long-term health outcomes have become more important.  Reported 5-year survival rate after pediatric LT in North America is >85%.  More data on long-term health consequences are provided in a review of 167 10-year survivors from a North American Database (Studies of Pediatric Liver Transplantation –SPLIT) (J Pediatr 2012; 160: 820-6).

Ng VL et al report on frequency of comorbidities as well as quality of life.  Of the 10-year survivors who were included in this study: 85 (50.9%) were transplanted in the first year of life; 69 (41.3%) received transplants between 1-7.9 years.  Biliary atresia accounted for 55.1% of the transplanted cohort; the remainder were due to the following: metabolic liver disease 23 (13.8%), acute liver failure 18 (10.8%), other cholestatic conditions 17 (10.2%), tumor 6 (3.6%), and other 11 (6.6%).

First allograft survival rates were 94% at 1 year and 88% at 10 years.   Health-related quality of life (HRQOL) as assessed by the PedsQL 4.0 Generic Core Scales revealed lower patient self-reported total scale scores for LT survivors compared with healthy children (77.2 vs 84.9, P<.001).  14% had HRQOL >2 SDs below that of a matched healthy population.  Other specific post-LT morbidities included the following:

  • Impaired linear growth (23% <10th percentile); ongoing steroid therapy was associated with increased risk of poor linear growth.
  • Renal dysfunction (9%) –defined as calculated glomerular filtration rate <90 mL/min/1.73 m2.
  • Hyperlipidemia: 20% with hypercholesterolemia, and 26% with hypertriglyciridemia
  • Lymphoproliferative disease (5%).  EBV seroconversion occurred in 46 (47%) of 97 who had been EBV-negative prior to LT.  25 (15%) developed symptomatic EBV infection.
  • School performance: 32 (23%) had repeated a grade or were held back at least 1 school year.
  • Liver fibrosis: at 10 years, elevated aminotransferases were noted in 11% and increased gamma gluatmyl transpeptidase in 15%.  Previous studies from SPLIT indicate fibrosis is common in long-term survivors even with good clinical outcomes.

Alive and well?  While survival has improved remarkably, better outcomes are still needed.

Related posts:

Picking winners and losers with liver transplantation allocation

Good care 24/7

Big gift, how much risk

Additional references:


  • -Pediatrics 2008; 122: 1128-35.  Outcomes of 461 pediatric LT.
  • -Am J Transplant 2008; 8: 2506-13.  Improving long-term outcomes of LT.
  • -Hepatolog 2009; 49: 880-6.  LT-Liver fibrosis at 10 year followup.
  • -JPGN 2008; 47: 165. ~50% below 1.3 SD of adult height. Many show partial catch up growth.
  • -Liver Transplant 2006; 12: 1310. Review article on nutrition for OLTx patient.

New caustic danger from detergent pods

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“Brightly colored little packets that combine laundry detergent with other cleaning agents are a new convenience for consumers — and a new danger for kids.”

See more complete story at attached links that follow:

http://www.washingtonpost.com/national/poison-control-centers-field-increased-number-of-calls-of-children-ingesting-detergent-packets/2012/05/24/gJQAaiSZnU_story.html

http://yourlife.usatoday.com/health/healthyperspective/post/2012-05-24/new-kid-danger-swallowing-candy-colored-laundry-packets/701134/1

Does pancreas divisum cause pancreatitis?

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The role of pancreas divisum (PD) as a cause of either acute recurrent or chronic pancreatitis (AR/CP) remains a matter of debate.  A recent study suggests that pancreas divisum serves as a cofactor but does not cause pancreatitis independently (Am J Gastroenterol 2012; 107: 311-17).

PD occurs due to failure of fusion of the dorsal and ventral pancreatic buds during gestation.  The frequency of PD has been estimated to be between 5-10% of the general population based on large post-mortem studies.  There is an increased frequency of PD in patients with idiopathic pancreatitis (12-26%).  The referenced study from France examined the frequency of genetic mutations vis-a-vis relationship with PD.  PD was determined using MRCP.

Findings–percentage with PD among subgroups:

  • 7% of subjects without pancreatic disease, n=45
  • 7% of alcohol-associated pancreatitis patients, n=29
  • 5% of idiopathic pancreatitis patients, n=40
  • 16% of patients with PRSS-1-associated pancreatitis, n=19
  • 16% of patients with SPINK-1-associated pancreatitis, n=25
  • 47% of patients with CFTR-associated pancreatitis, n=30

The study has several limitations.  Overall, the numbers of patients with pancreatitis are fairly low.  In addition, these genetic mutations are not typically examined in individuals without pancreatitis.  As such, the effect of these mutations with PD still is difficult to know in comparison to a larger population.

Additional references:

  • Recurrent pancreatitis and genetic underpinnings (previous blog post)
  • -Clin Gastro & Hep 2009; 7:141.  Review -case of recurrent pancreatitis -suggests checking ANA, Trig, IgG4 (also TTG)
  • – J Pediatr 2008; 152: 106.  Acute pancreatitis in young children; 109 cases.  systemic dz in 29, drugs in 7, gallstones in 3, annular pancreas in 1, trauma in 7, infections in 16, CF in 2, Idiopathic in 15.
  • -NEJM 2006; 354: 2142.  Review of acute pancreatitis mgt.
  • -Clin Gastro & Hep 2006; 4: 455.  Elevated pancreatic enzymes frequently identified in celiac disease.
  • -Clin Gastro & Hep 2007; 5: 1347. Celiac is a risk factor for acute & chronic pancreatitis. n=14,239 & 69,381 reference population (Sweden).
  • -Pediatrics 2005; 115: e463. CF & pancreatitis
  • -JPGN 2003; 37: 5591. Systemic dz 14%, Trauma 14%, drugs 12%, metabolic 6%, structural 5%, infectious 8%, ERCP 6%, Biliary 12%, Familial 3% (but accounted for 20% of episodes) Transplant 8%, idiopathic 8%
  • -Clin Perspectives in Gastro 2002; 5: 73. Pancreas divisum

A new GALD phenotype

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A previous post discusses gestational alloimmune liver disease (GALD) (The more you know the more you see) and provides a number of references.  Additional insight into GALD comes from a recent case report (Pediatrics 2012; 129: e1076-79).

In this report, ascites is recognized in utero at 29 weeks.  This ascites was determined to be due to compression of the vena cava by hypertrophy of the hepatic caudate lobe.  When the patient was delivered at 34 weeks gestation, additional testing revealed normal coagulation parameters, peak ferritin level of 750 ng/ml at day 19, and a nodular liver on ultrasonography.  The patient underwent a liver biopsy via minilaparotomy which confirmed cirrhosis but did not show evidence of iron overload.  Tests for a multitude of other liver diseases were negative.  Liver biopsy stains demonstrated C5b-9 complex in >95% of hepatocytes after treatment with monoclonal antibody.  The detection of a high level of C5b-9 neoantigen is highly specific for  GALD.  Clinically, the patient had spontaneous recovery.

Take home points:

1. While iron overload is a hallmark of GALD, it is likely a consequence and not a cause of this severe liver disease.

2. Identifying atypical GALD cases allows the institution of immunotherapy during future pregnancies which reduces the recurrence risk.

3. The phenotypic spectrum of GALD includes the following:

  • Neonatal liver failure with iron overload
  • Fetal liver failure and/or death with or without iron overload
  • Liver cirrhosis and mild neonatal liver disease without iron overload.  These patients likely require special stains (call Peter Whittington for these patients)

Quantifying Risk of PML with Natalizumab

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Given the limited number of treatment options for inflammatory bowel disease, when Natalizumab became available, there was a great deal of enthusiasm.  This quickly diminished as reports of progressive multifocal leukoencephalopathy (PML) emerged.  So far, I have not prescribed this agent.

Due to its efficacy for multiple sclerosis and IBD, there has been continued interest in understanding the risk for PML (NEJM 2012; 366: 1870-80, editorial pg 1938-39).

Key findings:

  • 212 cases of PML among 99,571 patients treated with natalizumab (2.1 cases per 1000)
  • Three main risk factors: positive JC-virus antibody, previous use of immunosuppressants, and receiving natalizumab more than 2 years

Patients who were negative for anti-JC virus antibodies had an incidence of 0.09 cases or less per 1000 patients.  Among patients who test positive for anti-JC virus antibodies, the risk remained <1 per 1000 patients if no use of immunosuppressants and 2 per 1000 if prior use of immunosuppressants during the first two years of therapy.  The risks were five-fold higher after 2 years in both groups.

While the risks are becoming more clear, the benefits of natalizumab are fairly well-established for multiple sclerosis.  Natalizumab decreased the annualized rate of relapse among patients with relapsing–remitting multiple sclerosis by 68%.

Additional references:

  • -NEJM 2009; 361: 1067, 1075, 1081.  Asymptomatic detection of JC virus common in urine noted in patients Rx’d with natalizumab (19% baseline to 63% on Rx); actual leukoencephalopathy ~1/1000 patients.
  • -Gastroenterol 2007; 132: 1672.  ENCORE trial.
  • -JPGN 2007; 44: 185. n=31 children/adolescents.  55% response, 29% remission; dosed at 3mg/kg.
  • -IBD 2007; 13: 2.  n=79.  Trial of combination natalizumab & infliximab.
  • -NEJM 2006; 354: 899, 911, 924.  Natalizumab slows progression of MS.  Risk of PML due to JC virus 1:1000 in 18 months of Rx.
  • -NEJM 2005; 353: 1912/1965.  Natalizumab not significantly effective for Crohn’s in this study
  • -NEJM 2005; 353: 362, 369, 375, 414.  3 cases of PML associated with Natalizumab
  • -JPGN 2004; 39: S49 [abstract 0107].  Natalizumab in 38 adolescents was effective (Hyams et al).
  • -Gastroenterol 2004; 126: 1574-81. review.  Natalizumab benefitted subjects with elevated CRP. (dosing 300mg every 4 weeks.)
  • -NEJM 2003; 24-32 & 68.  Natalizumab improved response rates in pts c Crohn’s dz (similar to infliximab).  Drug blocks alpha4 integrins which are required for lymphocytes to enter the intestine.
  • -Gastroenterol 2001; 121: 268-74. Infusion of 3mg/kg decreases CDAI in Crohn’s dz.