How Progressive Familial Intrahepatic Cholestasis (PFIC) Recurs After Liver Transplantation

A recent case-report study (D Krebs-Schmitt et al. JPGN 2019; 68: 169-74) describes how progressive familial intrahepatic cholestasis (PFIC) due to bile salt export pump (BSEP) deficiency can recur after liver transplantation.

BSEP deficiency due to mutations in ABCB11 gene causes the development of PFIC type 2.  In this case report, the authors describe recurrence of BSEP-deficiency following liver transplantaion in 3 patients.

Key points:

  • Following liver transplantation, patients with PFIC 2 can develop antibodies to BSEP as this antigen was not present in the pretransplant period.  Since initial reports, more than 20 patients have been described. “In most of these cases, intensifying the immunosuppression led to normalization of graft function.”
  • In this case report, the 3 patients ultimately required retransplantation due to recurrent disease and one patient died (following retransplantation). One patient also received stem cell transplantation after a complicated course.

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Clostridium difficile and Cannabis

Briefly noted:

W El-Matary et al. J Pediatr 2019; 206: 20-5.  This study from Manitoba using electronic database found that the incidence rate of C difficile was stable from 2005-2015, with an overall rate of 7.8 per 100,000 person-years.  Children with Hirschsprung’s and inflammatory bowel disease had increased prevalence rates.

JL O’Loughlin et al. J Pediatr 2019; 206: 142-7. Using data from two longitudinal studies in Montreal (Cannabis is legal for adults in Canada since 2018), the authors examined the rate of cannabis initiation starting in 6th grade through 11th grade. Key finding was that cannabis use was 1.8 time more likely among children whose parents used cannabis.  Overall, cannabis use increased from 3.1% in grade 6 to 25.7% in grade 11.

What is erythromelagia?  This term was noted in the title of a recent report (J Pediatr 2019; 206: 217-24) and refers to bilateral episodic pain and redness that occurs in feet, hands and occasionally the ears.  In some case, symptoms progress proximally to involve the legs, arms, and rarely the face.


Are Liver Tests Needed in Pediatric Patients Receiving Statin Therapy?

A recent study (NK Desai et al. JPGN 2019; 68: 175-81) showed excellent safety of statins with regard to hepatotoxicity. This study utilized prospectively collected ALT values from the Preventive Cardiology Program at Boston Children’s and their lipid program from 2010 until 2014.  They included 943 patients (mean age 14 years) with 111 always on statin, 97 started on statin, and 735 never on a statin.

Key findings:

  • In this cohort with dyslipidemia, there was no higher burden of ALT elevations among pediatric patients receiving statin therapy compared to those who did not receive statin therapy.
  • Patients with ALT values ≥5 times ULN were not increased among patients receiving statins (n=3) compared to those who did not receiving statins (n=13)
  • Mean ALT was actually greater in the non-statin cohort by 2 U/L but likely related to the increased frequency of obesity in the non-statin group.

My take: Due to the high prevalence of nonalcoholic fatty liver disease (NAFLD), it is likely that most patients who need statin therapy would get liver biochemistries; however, this study suggests that additional monitoring is not required in asymptomatic patients who receive statins for dyslipidemia.

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Prevalence of Anxiety, Depression, and Conduct Disorders

For any physician, it is easy to think that the entire world is sick since that is what we see all day long.  In a pediatric GI office, there are high rates of anxiety and depression. A recent study (RM Ghandour et al. J Pediatr 2019; 206: 256-67) shows that not everyone is afflicted.  Using data from the 2016 National Survey of Children’s Health (children 3-17 years), which relies on self-administered surveys, the authors found the following:

  • 7.1% had current anxiety problems
  • 7.4% had a current behavioral problem
  • 3.2% had current depression.
  • Nearly 3 of 4 children with depression had concurrent anxiety, whereas 1 in 3 children with anxiety had concurrent depression.

The study includes detailed tables examining age, gender, ethnicity, region of country, rural/urban, insurance status, financial status, educational attainment, and health status. While this study relies on parent/caregiver reports, the authors note that  “research has shown good agreement between parental report and clinical records.”

My take: Problems with anxiety, depression, and behavioral problems are common but not universal.

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AGA Guidelines on the Management of Mild-to-Moderate Ulcerative Colitis

A recent AGA Clinical Practice Guideline on the Management of Mild-to-Moderate Ulcerative Colitis was published along with patient guide (pg 766-67), a brief summary (pg 768) (“spotlight”) and technical review.

  • CW Ko et al. Gastroenterol 2019; 156: 748-64.
  • S Singh, JD Feuerstein et al. Gastroenterol 2019; 156: 769-808.

Summary of Recommendations for the medical management of mild-to-moderate ulcerative colitis: (available from AGA Website, my comments in blue & I bolded some of the recommendations):

1.    Use either standard dose mesalamine (2-3 grams/day) or diazo-bonded 5-ASA [Balsalazide or Olsalazine] rather than low dose mesalamine, sulfasalazine or no treatment in patients with extensive mild-moderate UC. (Strong recommendation, moderate quality evidence) [The article notes several potential exceptions for sulfasalazine: doing well on current treatment, prominent arthritic symptoms, or cost]

2.    In patients with extensive or left-sided mild-moderate UC, add rectal mesalamine to oral 5-ASA. (Conditional recommendation, moderate quality evidence)

3.    In patients with mild–moderate UC with suboptimal response to standard-dose mesalamine or diazo-bonded 5-ASA or with moderate disease activity, use high-dose mesalamine (>3 g/d) with rectal mesalamine. (Conditional recommendation, moderate-quality evidence [induction of remission], low-quality evidence [maintenance of remission])

4.    In patients with mild–moderate UC being treated with oral mesalamine, use once-daily dosing rather than multiple times per day dosing. (Conditional recommendation, moderate quality evidence) [In the commentary, the authors note that 4 RCTs have shown no differences when using equivalent dose once a day compared to divided dose and that once a day promotes adherence]

5.    In patients with mild–moderate UC, use standard-dose oral mesalamine or diazo-bonded 5-ASA, rather than budesonide MMX or controlled ileal-release budesonide for induction of remission. (Conditional recommendation, low quality of evidence)

6.    In patients with mild–moderate ulcerative proctosigmoiditis or proctitis, use mesalamine enemas (or suppositories) rather than oral mesalamine. (Conditional recommendation, very-low-quality evidence) [In commentary, the authors note that oral mesalamine can be given based on patient preference, but that for distal disease there is likely a higher response with topical therapy]

7.    In patients with mild–moderate ulcerative proctosigmoiditis who choose rectal therapy over oral therapy, use mesalamine enemas rather than rectal corticosteroids.(Conditional recommendation, moderate-quality evidence)

8.    In patients with mild–moderate ulcerative proctitis who choose rectal therapy over oral therapy, use mesalamine suppositories. (Strong recommendation, moderate-quality evidence)

9.    In patients with mild–moderate ulcerative proctosigmoiditis or proctitis being treated with rectal therapy who are intolerant of or refractory to mesalamine suppositories, use rectal corticosteroid therapy rather than no therapy for induction of remission. (Conditional recommendation, low-quality evidence)

10.    In patients with mild–moderate UC refractory to optimized oral and rectal 5-ASA, regardless of disease extent, add either oral prednisone or budesonide MMX. (Conditional recommendation, low-quality evidence)

11.    In patients with mild–moderate UC , AGA makes no recommendation for use of probiotics. (No recommendation, knowledge gap)

12.    In patients with mild–moderate UC despite 5-ASA therapy, AGA makes no recommendation for use of curcumin. (No recommendation, knowledge gap)

13.    In patients with mild–moderate UC without Clostridium difficile infection, AGA recommends fecal microbiota transplantation be performed only in the context of a clinical trial. (No recommendation for treatment of ulcerative colitis, knowledge gap)

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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

Joshua Tree National Park, Hike to Warren Peak