Antivirals Reduce Vertical Transmission of Hepatitis B

Posted on by
Chelsea Market, NYC

Chelsea Market, NYC

The latest study that shows antivirals interrupt hepatitis B viral (HBV) transmission from mother-to-infant: H-L Chen et al. Hepatology 2015; 62: 375-86.

In this open-label, non-randomized controlled study from Taiwan, the researchers recruited women to receive tenofovir (TDF) at a dose of 300 mg once a day (n=62), initiated from gestational age 30-32 weeks until 1 month following delivery, and compared them to a control group (n=56).  There were high levels of viremia with HBV DNA ≥7.5 log10 IU/mL. All infants received HBV vaccination and HBIG within 24 hours of birth.

Key findings:

  • Infant transmission of HBV was reduced: at 6 months of age, infant HBsAg positivity was 1.54% versus 10.71%, P=0.0481).  At delivery, HBV DNA positivity was noted in 6.15% compared with 31.48% of the control group.
  • Maternal ALT was improved in the TDF group. ALT elevation more than two times the upper limit of normal for ≥3 months occurred in 3.23% compared with 14.29% of controls.
  • Adverse effects: only mild to moderate (self-limited) gastrointestinal and skin symptoms were noted. No fetal abnormalities were identified.

Bottomline: Antivirals, including both tenofovir and telbivudine, reduce vertical HBV transmission with a favorable safety profile.  The use of antivirals is complementary to standard prevention which consists of providing Hepatitis B immune globulin and Hepatitis B vaccine to infants of HBV-infected pregnant women within 12 hours of birth.

Related blog posts:

Celiac Update September 2015

Posted on by

A useful review (CP Kelly et al. Gastroenterol 2015; 148: 1175-86) summarizes the ‘state of the art” information regarding celiac disease presentation and management. The review notes that some expert organization consensus state that intestinal biopsy is mandatory whereas some do not under certain conditions.

According to ESPGHAN, if anti-TTG >10-fold elevated, anti-EMA positive in separate sample, and +HLA typing, then a biopsy may not be required.  For the WGO (World Gastroenterologic Organization), the exception focuses on available local resources.

The article recommends the following for monitoring:

  • Clinical evaluation -annually or if recurrent symptoms
  • Serology & Nutritional evaluation -every 3-6 months until normal, then every 1-2 years.  Common nutrient deficiencies: iron, vitamin D, vitamin B12, folate, and zinc
  • Bone density -once within first 2 years.  (Some recommend checking after 1 year on gluten free diet)
  • Liver transaminase levels & Thyroid function tests -at diagnosis, then every 1-2 years.  Autoimmune thyroid disorders are “found in approximately 15-20% of adults with celiac disease”

A second retrospective indicates that ESPGHAN criteria for avoiding biopsy in children and adolescents with high titers for anti-TTG (>10-fold) along with positive EMA, and HLA-DQ2/DQ8.are reasonable.  Here’s the abstract:

Are ESPGHAN “Biopsy-Sparing” Guidelines for Celiac Disease also Suitable for Asymptomatic Patients?

CM Trovato, et al.The American Journal of Gastroenterology , (15 September 2015) | doi:10.1038/ajg.2015.285

OBJECTIVES:

In 2012, European Society of Pediatric Gastroenterology, Hepatology, and Nutrition published novel guidelines on celiac disease (CD) diagnosis. Symptomatic children with serum anti-transglutaminase (anti-tTG) antibody levels ≥10 times upper limit of normal (ULN) could avoid duodenal biopsies after positive HLA test and serum anti-endomysial antibodies (EMAs). So far, both asymptomatic and symptomatic patients with anti-tTG titer <10 times ULN should undergo upper endoscopy with duodenal biopsies to confirm diagnosis. The aim of this study was to assess the accuracy of serological tests to diagnose CD in asymptomatic patients.

METHODS:

We retrospectively reviewed data of 286 patients (age range: 10 months to 17 years) with CD diagnosis based on elevated titer of anti-tTG, EMA positivity, and histology. All patients were distinguished between symptomatic and asymptomatic; histological lesions were graded according to the Marsh–Oberhuber (MO) criteria. Fisher exact test was applied to analyze both groups in terms of diagnostic reliability of serological markers.

RESULTS:

A total of 196 patients (68.53%) had anti-tTG titers ≥10 times ULN. Among them, a group of 156 patients (79.59%) also had symptoms suggestive of CD (“high-titer” symptomatic); of these, 142 patients (91.02%) showed severe lesion degree (3a, 3b, 3c MO). Conversely, 40 out of 196 patients (20.40%) were asymptomatic (“high-titer” asymptomatic) and 37 patients (92.5%) of them showed severe lesion degree (3a, 3b, 3c MO). No difference in histological damage was found between “high-titer” symptomatic and “high-titer” asymptomatic children (Fisher exact test, P=1.000).

CONCLUSIONS:

If confirmed in large multicenter prospective studies, the “biopsy-sparing” protocol seems to be applicable to both symptomatic and asymptomatic patients with anti-tTG titer ≥10 times ULN, positive EMA, and HLA-DQ2/DQ8.

Related blog posts:

 

 

Celiac Disease: “Ten Things That Every Gastroenterologist Should Know”

Posted on by

Turns out that a recent review (AS Oxentenko, JA Murray. Clin Gastroenterol Hepatol 2015; 13: 1396-1404) is a succinct summary on celiac disease with questions focused on diagnosis, endoscopy, genetics/HLA typing, at risk groups, management, adherence, non responsive celiac patient, and refractory patients.  Most of these topics have been addressed previously on this blog.

However, here are a few pointers:

  • “Histologic improvement is slow in adults…Mucosal recovery, defined by a villous:crypt ratio of 3:1, was present in 34% at 2 years and 66% at 5 years, with healing complete in 90% by 9 years.”
  • “Mucosal recovery is faster and more complete in children, with 95% recovery in 2 years and 100% recovery long-term in children following a GFD.”
  • With nonresponsive celiac disease, “defined as a lack of response to 6 months on a GFD or a recurrence of celiac-related features despite compliance,” the authors recommend reviewing serology and biopsies.  Other etiologies to consider include bacterial overgrowth, autoimmune enteropathy, tropical sprue, Crohn’s disease, combined variable immunodeficiency, collagenous sprue, and eosinophilic gastroenteritis.
  • For refractory celiac disease with ongoing villous atrophy, this “should prompt immunophenotyping and T-cell rearrangement studies” of duodenal biopsies.

Briefly noted: ET Jensen et al. Clin Gastroenterol Hepatol 2015; 13: 1426-31.  The authors examined 88,517 patients who had undergone both esophageal and duodenal biopsies.  “Odds of EoE (eosinophilic esophagitis) were 26% higher in patients with celiac disease than in patients without celiac disease” (adjusted odds ratio 1.26).

Related blog posts:

From the High Line, NYC

From the High Line, NYC

“The Solution to Drug Prices”

Posted on by

Worth a read: “The Solution to Drug Prices” by Eziel Emanuel

An excerpt:

WE’RE paying too much for prescription drugs….Despite representing about 1 percent of prescriptions in 2014, these types of high-cost drugs accounted for some 32 percent of all spending on pharmaceuticals….

Almost all developed countries… making drugs available at fixed prices …Drug companies would immediately raise two objections: the high risks associated with drug development and, related, the high cost of research and development. But both of these arguments are fatuous…

Also, as outrageous as they are, prices are not the real issue. Value is. What really frustrates people are expensive drugs that do not provide a cure. For instance, Opdivo adds an average of 3.2 months of life to lung cancer patients and costs $150,000 per year for treatment…

Everyone, including drug company executives, believes that high prices cannot continue. Indeed, that is one reason that companies are trying to maximize profits while they can. We must come up with a comprehensive solution now.

Parenteral Nutrition and False Positive Newborn Screens, Plus One

Posted on by

Briefly noted:

“Stopping Parenteral Nutrition for 3 Hours Reduces False Positives in Newborn Screening” T Tim-Aroon et al. J Pediatr 2015; 167: 312-6. By stopping parenteral nutrition (PN), the authors reduced false-positive results for amino acid disorders among newborn screenings. In patients receiving PN, holding PN (and using IVFs) was associated with a false-positive rate of 2/65 compared with 29/245 who continued PN (3.1% vs. 11.8%; P=.037)

“Age at Weaning and Infant Growth: Primary Analysis and Systemic Review” B Vail et al. J Pediatr 2015; 167: 317-24. UK prospective study with n=571 singletons along with systemic review which identified two trials. Conclusion: “In high-income countries, weaning between 3 and 6 months appears to have a neutral effect on infant growth.  Inverse associations are likely related to reverse causality.”

 

 

Just Saying…Vaccines Don’t Trigger Inflammatory Bowel Disease

Posted on by

The other day I was having a fun discussion on words that we may choose before providing information that others might not like.  Some examples:

  • “No offense but”…
  • “Don’t take this the wrong way”…
  • “Just saying”…

A recent report (GP de Chambrun et al. Clin Gastroenterol Hepatol 2015; 13: 1405-15) debunks claims that vaccines increase the risk of inflammatory bowel disease (IBD).  A report by Thompson NP et al (Lancet 1995; 345: 1071-74) suggested that measles vaccination could increase risk of IBD.  In the current study, the researchers examined 11 previous studies for review and meta-analysis.  Vaccines included: BCG, DPT, smallpox, poliomyelitis, pertussis, H1N1,measles, mumps, rubella, and combined MMR.  This study included 2399 patients with IBD and 33,747 controls. Bottomline: “Results of this meta-analysis show no evidence supporting an association between childhood immunization or H1N1 vaccination in adults and risk of developing IBD.” With regard to the measles vaccine in particular, the relative risk was 1.33 (CI 0.31 -5.80) in cohort studies and the relative risk was 0.85 (CI 0.60 -1.20) in case-control studies.

What types of words do you hear people use before saying something someone is not going to like?

Related posts:

Desperate Measures in Refractory IBD

Posted on by

The often cited, ‘desperate times call for desperate measures,’ resonates in the setting of refractory inflammatory bowel disease (IBD).  [Of course, this saying could be used to justify about anything you want to do.]  For IBD, two recent studies point out potential remedies:

  • SA Merkley, et al. Inflamm Bowel Dis 2015; 21: 1854-59.
  • M Lazzerini, et al. Inflamm Bowel Dis 2015; 21: 1739-49, with editorial by A Bousvaros (1750-51)

In the first study, the authors retrospectively analyzed date from 24 IBD patients who were treated with intravenous immunoglobulin (IVIG) at a dose of 0.4 g/kg/day for 3 days, then 0.4 g/kg once a month. Key findings: 16 (67%) had a response and 3 (12.5%) obtained remission. Measures of improvement included CRP, ESR, Simple Endoscopic Score for Crohn’s disease, and the Harvery-Bradshaw Index. The researchers speculate that IVIG has anti-inflammatory and immunomodulator effects.  In addition, they note that IVIG can be given with concurrent infections.

In the second study, the authors studied thalidomide(1.5-2.5 mg/kg/day) in a double-blind, placebo-controlled randomized pediatric clinical trial in children with refractory active ulcerative colitis. Key findings: at week 8, clinical remission was achieved in 10/12 (83%) of thalidomide arm compared with 2/11 (19%) of control patients.  Then, among control patients who were switched, 8 of 11 (72%) reached remission as well. Peripheral neuropathy and amenorrhea were reported adverse effects. In the accompanying editorial, Dr. Bousvaros notes that there has been some data to suggest thalidomide efficacy in ulcerative colitis since 1979.  However, due to widespread bad publicity related to thalidomide-induced teratogenicity (eg. phocomelia) and side effects including neuropathy, it has not been used with much frequency. He notes that this study, as well, requires replication and speculates that “the primary focus on drug development will focus on newer small molecules and biologics, and this potentially useful medication may be left on the sidelines.” It is worth noting that the authors response (pg 1752) to this editorial was that the stigma of thalidomide is unwarranted and that teratogenicity can be avoided. “No case was observed out of 124,000 patients enrolled in the thalidomide distribution risk management program for more than 6 years.”

Bottomline: Both thalidomide and IVIG may be beneficial to desperate patients (and desperate doctors).  While small trials appear promising, larger trials are needed.  Don’t hold your breath waiting … will they ever happen?

Related blog posts:

ICD-10: Source for humor?

Posted on by

Like most physicians, I am not terribly excited about the transition to ICD-10.  The increased detail with coding will take longer and be a hassle. However, there is apparently some humor to be derived from the institution of ICD-10.

From HealthcareDive.com: “There are 68,000 billing codes under the new ICD-10 system, as opposed to a paltry 13,000 under the current ICD-9. …Despite the controversy surrounding ICD-10, there is one universally agreed-upon upside to the hyper-specific coding system: Weird and obscure codes that stand for bizarre medical injuries. There’s even an illustrated book, Struck by an Orca: ICD-10 Illustrated.”

Some of the absurd ICD-10 codes from HealthcareDive.com:

  • V97.33XD: Sucked into jet engine, subsequent encounter
  • Y92.146: Swimming-pool of prison as the place of occurrence of the external cause
  • W55.41XA: Bitten by pig, initial encounter​
  • W61.62XD: Struck by duck, subsequent encounter
  • Z63.1: Problems in relationship with in-laws
  • W220.2XD: Walked into lamppost, subsequent encounter
  • Y93.D: V91.07XD: Burn due to water-skis on fire, subsequent encounter​
  • W55.29XA: Other contact with cow, subsequent encounter
  • W22.02XD: V95.43XS: Spacecraft collision injuring occupant, sequela
  • W61.12XA: Struck by macaw, initial encounter
  • R46.1: Bizarre personal appearance

Multiple authorities have weighed in on the issue of which ICD-10 codes are most zany. Here are a few links:

University of South Florida their list includes

  • Knitting and Crocheting (Y93.D1)
  • Pecked by chicken, initial encounter (W61.33XA)

Multibriefs Exclusive their list includes

  • T71.231D Asphyxiation due to being trapped in a discarded refrigerator, accidental
  • V80.730A Animal-rider injured in collision with trolley
  • Z62.1 Parental overprotection
  • T63 Unspecified event, undetermined intent

NY Times: Roughed up by an Orca? There’s a code for that (from 12/29/13) “There are codes for injuries incurred in opera houses and while knitting, and one for sibling rivalry.” This article has some nice graphics, including one of a water skier with the skis on fire.

Another Look at “Step-up” IBD Therapy

Posted on by

Whether and how long to continue immunomodulators in patients who have undergone a “step-up” treatment to anti-tumor necrosis factor (anti-TNF) therapy remains murky.  This is due to conflicting data from different patient cohorts, changing treatment trends, (e.g. use of drug monitoring to enhance anti-TNF therapy), and different endpoints. With regard to the latter, dual therapy has been clearly more effective in some landmark studies (eg. SONIC, UC SUCCESS); however, there have been ongoing concerns regarding long-term outcomes and adverse effects.

Will more studies help resolve this question? Perhaps, but not today.

A recent study (MT Osterman et al. Clin Gastroenterol Hepatol 2015; 13: 1293-1301) examined a retrospective cohort of new users of anti-TNF therapy for Crohn’s disease in Medicare recipients.  The authors matched 381 combination with infliximab (ie. dual therapy) with 912 users of monotherapy. In addition, the authors did the same with adalimumab with 196 combination users and 505 monotherapy users. In their cohort, combination therapy occurred primarily as a “step-up” treatment after institution of thiopurine therapy.

Results:

  • Key outcome measures were unchanged: rates of surgery (hazard ratio [HR] 1.2, hospitalization HR 0.82, discontinuation of anti-TNF therapy or surgery HR 1.09, and serious infection HR 0.93
  • Opportunistic infections were increased in combination therapy with HR 2.64 and herpes zoster infection was increased with HR 3.16

Take-home message: This study suggests, at least in this elderly population, that once remission is achieved with anti-TNF therapy, discontinuation of thiopurine therapy or use of an alternative immunomodulator therapy may be worthwhile.  At the same time, definitive answers to these type of questions await carefully designed randomized trials.

Related blog posts:

Identifying Anastomotic Ulcers with Capsule Endoscopy

Posted on by

A retrospective review (LM Bass et al. JPGN 2015; 61: 215-9) showed that capsule endoscopy (CE) can be helpful in identifying anastomotic ulcers among patients with short bowel syndrome and chronic GI blood loss.

This study of 4 patients (& 6 CE procedures) indicated that two of these patients underwent surgery after identifying anastomotic ulcers.  The other common treatment was antibiotics. In the suggested evaluation CE was used after upper/lower endoscopy. The recommended role for patency capsule/small bowel imaging is not clearly spelled out, but should be carefully considered due to the risk of strictures.

“The decision to perform CE is made in conjunction with medical and surgical teams so that, although every effort is made to avoid a situation that may result in a retained capsule, both parents and care teams are prepared.”

Related blog posts: