Phase 3 Trial of Sebelipase Alfa for Lysosomal Acid Lipase Deficiency

Posted on by

A recent report (BK Burton et al. NEJM 2015; 373: 1010-20, editorial 1071-1) provides preliminary evidence of efficacy of Sebeliplase Alfa for lysosomal acid lipase deficiency.

In this multicenter, randomized, double-blind, placebo-controlled study of 66 patients, enzyme replacement therapy with Sebelipase alfa was examined (1 mg intravenously every other week).  After 20 weeks, all patients were treated by open-label. Of the 32 patients who had had liver biopsies, 10 (31%) were noted to have cirrhosis.

Findings:

  • Alanine aminotransferase normalized in 11 (36%) of treated patients compared with 2 (7%) of controls
  • Improvement in lipid levels and reduction in hepatic fat content were evident in treated patients (P<0.001 for all comparisons, except P-0.04 for triglycerides

The editorial provides a schematic explaining how sebelipase alfa targets the hepatocyte (Figure 1).  The authors note that “longer-term follow-up in a larger number of patients will be required for confirmation.”

Related blog post:

How Much Morphine Should Be Prescribed?

Posted on by

In comparison to other medications, opioid pain medications are more carefully regulated, have the potential for more severe adverse reactions, and written prescriptions are needed for dispensing. So, trying to provide the right amount is a little tricky. With this background, a recent study (M Aboud-Karam et al. J Pediatr 2015; 167: 599-604) examines the use of morphine after pediatric surgery.

This prospective study included 243 subjects. Findings:

  • 56% of participants who received a scheduled (“regular basis”) prescription administered the medication as ordered.  The most common reason for deviation was a lack of pain or mild pain relieved by acetaminophen.  33 of the 104 patients who received a scheduled prescription did not even pick up the medication from the pharmacy.
  • 85% of participants in the “as needed” prescription group were administered morphine as ordered; however, 76% of this group took two or fewer doses. In this “as needed” group, a subset of 77 participants had precise data about the amount of morphine that they received.  Less than 10 % of the prescription doses available were administered.

The authors note that morphine is covered in Canada by both private and government-based insurance plans such that there are unlikely to be financial constraints limiting medication usage.  They note that the unused medication is a safety hazard due to potential for accidental ingestions.

My take: this study suggests that prescriptions with fewer doses of morphine may be warranted.

Related blog posts:

HCV Update -Fall 2015

Posted on by

Briefly noted:

S Naggie et al. NEJM 2015; 373; 705-13.  Among patients coinfected with HIV-1 and HCV (genotypes 1 and 4), 12 weeks of ledpasvir and sofosbuvir resulted in a 96% sustained HCV virological response.

DL Wyles et al. NEJM 2015; 373; 714-25.  Among patients coinfected with HIV-1 and HCV (genotype 1), 12 weeks of daclatasvir plus sofosbuvir resulted in a 97% sustained HCV virological response.

HA Innes et al. Hepatology 2015; 62: 355-64. Review of a Scottish HCV clinical database showed that a sustained viral response was associated with a reduced liver mortality (adjusted Hazard Ratio 0.24), a reduced non liver mortality (aHR 0.24) and reduced behavioral events (eg. violence-related injury aHR 0.51).  The latter improvement suggests that HCV eradication leads to healthier lives.

Also, seeing as today is ICD-10 Rollout: ICD-10: Source for humor? | gutsandgrowth

View from Signal Lodge, Grand Tetons

View from Signal Lodge, Grand Tetons

Useful Information on Eosinophilic Disorders

Posted on by

A review (JB Wechsler et al. J Asthma Allergy 2014; 7: 85-94) provides practical advice on dietary management of eosinophilic esophagitis (EoE); the section on food reintroduction from elemental diets for patients with EoE is particularly helpful.  They start with typically less allergenic foods (group A) to most allergenic (group D) -from their Table 2:

Group A:

  • Vegetables (nonlegume): carrots, squash, sweet potato, white potato, string beans, broccoli, lettuce, beets, asparagus, cauliflower, Brussel sprouts
  • Fruit (noncitrus, nontropical) apples, pear, peaches, plum, apricot, nectarine, grape, raisins
  • Vegetables: tomatoes, celery, cucumber, onion, garlic, and other vegetables

Group B

  • Citrus fruit: orange, grapefruit, lemon, lime
  • Tropical fruit: banana, kiwi, pineapple, mango, papaya, guava, avocado
  • Melons: honeydew, cantaloupe, watermelon
  • Berries: strawberry, blueberry, raspberry, cherry, cranberry

Group C

  • Legumes: lima beans, chickpeas, white/black/red beans
  • Grains: oat, barley, rye, other grains
  • Meat: lamb, chicken, turkey, pork

Group D

  • Fish/shellfish
  • Corn
  •  Peas
  • Peanut
  • Wheat
  • Beef
  • Soy
  • Egg
  • Milk

Also, this review includes a long list of “freebie” foods allowed while on elemental diet, including artificial flavors/colors, corn syrup, oils, salt, crystal lite, and many others.

The authors note that “in our practice, the period of exclusive elemental formula is limited to 4 weeks prior to therapeutic assessment by endoscopy and reintroduction…Single foods are introduced every 5-7 days” within a group and then endoscopy after 3-4 foods are clinically tolerated.”  Foods from groups C and D are introduced more cautiously.

Also noted: HM Ko et al. Am J Gastroenterol 2014; 109: 1277-85.  This retrospective study of 30 children with severe gastric eosinophilia (mean age 7.5 years) provides a good deal of useful information.  Key point: “the disease is highly responsive to dietary restriction therapies.”  82% of patients responded to dietary restrictions and 78% had a histologic response as well.  Dietary treatments included amino acid-based diet in 6 (n=6), 7-food group empiric diet (n=6), and empiric avoidance of 1-3 foods (n=5).  Pharmacologic treatments (proton pump inhibitor or cromolyn) were attempted in a total of four patients in this series with half responding clinically and one of four responding histologically.

Related blog posts:

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.

Biliary Dyskinesia –“Only in America”

Posted on by

In a recent commentary from Gastroenterology & Endoscopy News (http://www.gastroendonews.com), Moshe Schein reviews a recent study regarding biliary dyskinesia (BD) (Am J Surg 2015; 209: 799-803) which highlights that almost 20% of cholecystectomies in the U.S. are for noncalculous disease.

Key points:

  • The number of cholecystectomies for BD increased from 43.3 to 89.1 per 1 million between 1991-2011.
  • BD is “almost unheard of” in all other parts of the world.  “The majority of surgeons practicing outside the United States maintain that BD is a myth…Measuring gallbladder ejection fraction is something that they never do.”

My take: this is an area in need of a large randomized controlled trial.  Perhaps biliary dyskinesia will share the same fate as sphincter of Oddi dysfunction.

Related blog posts:

Jenny Lake, Grand Tetons

Jenny Lake, Grand Tetons

.

 

 

Guest Blogger Needed

Posted on by

I am looking for a colleague who will be attending this year’s NASPGHAN meeting who may be interested in being a “guest blogger” since I will not be going.  Ideally, this person has been in practice for several years.  In previous years, I have taken notes at the postgraduate course and the meeting. I’ve tried to provide some important teaching points without repeating the obvious.

If you are interested, please send me an email to jjhochman@gmail.com with your contact information and we can work on the logistics.  This is an opportunity to keep your colleagues who are unable to attend updated along with a wider audience.  Currently, there are more than 600 followers of this blog.  Any content posted would be properly attributed.  Some examples of previous posts:

Acid Suppression/C difficile and Adrenal Suppression/Topical Steroids

Posted on by

Briefly noted:

J Jimenez et al. (JPGN 2015; 61: 208-11) provide more data that gastric acid suppression is associated with an increase risk of Clostridium difficile infection (CDI). This was a retrospective case-control study with 138 children with CDI and 276 controls. After adjustment, acid-suppression therapy had a 1.8 Odds Ratio association with CDI.

S Harel et al. (JPGN 2015; 61: 190-3) in this retrospective ‘pilot’ study of  patients receiving topical budesonide for eosinophilic esophagitis, 6 of 14 (43%) had mild biochemical evidence of adrenal suppression, as measured by ACTH testing. Bottomline: a prospective study is likely needed to confirm or refute these findings. In the meanwhile, stress steroid coverage could be considered in patients on prolonged budesonide.

Coffee and Caffeine Associated With Less Fibrosis Among Patients with Hepatitis C

Posted on by

Perhaps I need to start drinking coffee.  In the absence of smoking or alcohol, it is reported to have a number of benefits. A recent study (N Khalaf et al. Clin Gastroenterol Hepatol 2015; 13: 1521-31) found that a “modest daily caffeine intake (as little as 100 mg) may protect against advanced hepatic fibrosis in men with chronic HCV infection.” This cross-sectional study of veterans with chronic HCV looked at 910 patients.  Patients were divided into controls with mild fibrosis (F0-F3) based on FibroSURE compared with those with F3/F4-F4 advanced fibrosis.  FibroSURE estimates are based on an algorithm which incorporates α2-macroglobulin, apolipoprotein A1, haptoglobin, total bilirubin, γ-glutamyl -transpeptidase, and alanine amiontransferase. Key findings:

  • Caffeinated coffee was higher among controls than those with advanced fibrosis (1.37 vs 1.05 cups/d, P=.038)
  • Overall caffeine ingestion was also higher in the controls; 66% of controls consumed >100 mg/day compared with 58% of those with advanced fibrosis.

Limitation: observaitonal, retrospective study with self-reported coffee/caffeine consumption. Related blog posts:

Screen Shot 2015-08-23 at 9.25.15 PM

NASH Update -September 2015

Posted on by

Briefly noted:

Obeticholic acid, a Farnesoid X Receptor Ligand, is being studied as a potential agent in nonalcoholic steatohepatitis (NASH).  According to a recent study (Lancet 2015; 385: 956-65), patients assigned to receive obeticholic acid were more likely to have improved liver histology compared with placebo (50/110 [45%] compared with 23/109 [21%]).  The  obeticholic group had increase serum cholesterol and LDL cholesterol. This study looked at a subgroup of patients in the FLINT study who had undergone liver biopsies.

E Vilar-Gomez et al. Gastroenterol 2015; 149: 367-78. This prospective study of 293 patients with histologically-proven NASH were followed after undergoing lifestyle changes for 52 weeks. At week 52, 88 subjects (30%) had lost ≥5% of their weight.  Degree of weight loss was independently associated with improvements in all NASH-related histologic parameters (steatohepatitis, NAS activity score, and fibrosis.

G Lassailly et al. Gastroenterol 2015; 149: 379-88. Between 1994-2013, 109 morbidly-obese patients with histologically-proven NASH underwent bariatric surgery.  One year after surgery, NASH had disappeared from 85% of the patients.

P Angulo et al. Gastroenterol 2015; 149: 389-97. In this retrospective analysis of 619 patients with NAFLD (1979-2005), the authors noted that “fibrosis stage, but no other histologic features of steatohepatitis, were associated independently with long-term overall mortality, liver transplantation, and liver-related events.”