Author Archives: gutsandgrowth

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About gutsandgrowth

I am a pediatric gastroenterologist at GI Care for Kids (previously called CCDHC) in Atlanta, Georgia. The goal of my blog is to share some of my reading in my field more broadly. In addition, I wanted to provide my voice to a wide range of topics that often have inaccurate or incomplete information. Before starting this blog in 2011, I would tear out articles from journals and/or keep notes in a palm pilot. This blog helps provide an updated source of information that is easy to access and search, along with links to useful multimedia sources. I was born and raised in Chattanooga. After graduating from the University of Virginia, I attended Baylor College of Medicine. I completed residency and fellowship training at the University of Cincinnati at the Children’s Hospital Medical Center. I received funding from the National Institutes of Health for molecular biology research of the gastrointestinal tract. During my fellowship, I had the opportunity to work with some of the most amazing pediatric gastroenterologists and mentors. Some of these individuals included Mitchell Cohen, William Balistreri, James Heubi, Jorge Bezerra, Colin Rudolph, John Bucuvalas, and Michael Farrell. I am grateful for their teaching and their friendship. During my training with their help, I received a nationwide award for the best research by a GI fellow. I have authored numerous publications/presentations including original research, case reports, review articles, and textbook chapters on various pediatric gastrointestinal problems. In addition, I have been recognized by Atlanta Magazine as a "Top Doctor" in my field multiple times. Currently, I am the vice chair of the section of nutrition for the Georgia Chapter of the American Academy of Pediatrics. In addition, I am an adjunct Associate Clinical Professor of Pediatrics at Emory University School of Medicine. Other society memberships have included the North American Society for Pediatric Gastroenterology Hepatology and Nutrition (NASPGHAN), American Academy of Pediatrics, the Food Allergy Network, the American Gastroenterology Association, the American Association for the Study of Liver Diseases, and the Crohn’s and Colitis Foundation. As part of a national pediatric GI organization called NASPGHAN (and its affiliated website GIKids), I have helped develop educational materials on a wide-range of gastrointestinal and liver diseases which are used across the country. Also, I have been an invited speaker for national campaigns to improve the evaluation and treatment of gastroesophageal reflux disease, celiac disease, eosinophilic esophagitis, hepatitis C, and inflammatory bowel disease (IBD). Some information on these topics has been posted at my work website, www.gicareforkids.com, which has links to multiple other useful resources. I am fortunate to work at GI Care For Kids. Our group has 17 terrific physicians with a wide range of subspecialization, including liver diseases, feeding disorders, eosinophilic diseases, inflammatory bowel disease, cystic fibrosis, DiGeorge/22q, celiac disease, and motility disorders. Many of our physicians are recognized nationally for their achievements. Our group of physicians have worked closely together for many years. None of the physicians in our group have ever left to join other groups. I have also worked with the same nurse (Bernadette) since I moved to Atlanta in 1997. For many families, more practical matters about our office include the following: – 14 office/satellite locations – physicians who speak Spanish – cutting edge research – on-site nutritionists – on-site psychology support for abdominal pain and feeding disorders – participation in ImproveCareNow to better the outcomes for children with inflammatory bowel disease – office endoscopy suite (lower costs and easier scheduling) – office infusion center (lower costs and easier for families) – easy access to nursing advice (each physician has at least one nurse) I am married and have two sons (both adults). I like to read, walk/hike, bike, swim, and play tennis with my free time. I do not have any financial relationships with pharmaceutical companies or other financial relationships to disclose. I have helped enroll patients in industry-sponsored research studies.

Eliminating sweetened beverages to help obesity

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For every difficult problem there’s a solution that’s simple, neat and wrong.–HL Mencken

Two studies from the New England Journal of Medicine, thus far (at the time of writing) published only online, shed some light on the difficult problem of consumption of sugar-sweetened beverages and its relationship to obesity:

  • A Trial of Sugar-free or Sugar-Sweetened Beverages and Body Weight in Children. Janne C. de Ruyter, M.Sc., et al. September 21, 2012DOI:  10.1056/NEJMoa1203034

  • A Randomized Trial of Sugar-Sweetened Beverages and Adolescent Body Weight. Cara B. Ebbeling, Ph.D., et al,  September 21, 2012DOI:  10.1056/NEJMoa1203388

The first study was an 18-month double-blind, randomized, controlled trial with 641 primarily normal-weight children between 4-12 years of age; patients were recruited from elementary schools.  Patients either received a sugar-free artificially sweetened beverage or a similar sugar-containing beverage, 8 oz per day at school.  At 18 months, 74% continued consuming these beverages; among those remaining in the program, on average, they consumed 83% of the assigned 7 cans each week.  Another marker of adherence was increased urinary sucralose in the sugar-free group (6.7 mg/L compared with 0.1 mg/L in the sugar group). Weight gain was less in the sugar-free group: 6.35 kg compared with 7.37 kg.  Other measures of weight gain were less as well, including skinfold-thickness, waist-to-height ratio, and fat mass. It is also noted that in the U.S. the average consumption of sweetened beverages is three times the amount noted in this Dutch study.

The second study examined 224 overweight and obese adolescents who were randomly assigned into experimental and control groups.  The experimental group received a 1-year intervention designed to decrease consumption of sugar-sweetened beverages; they were followed for an additional year afterwards.  Retention rates were good: 93% at 2 years. To support the experimental group, sugar-free beverages were delivered to  the house and the families received monthly motivational calls. In addition, patients had three check-in visits and written materials. The consumption of sugar-sweetened beverages declined in the experimental group from a baseline of 1.7 servings per day to nearly 0 at 1 year & remained lower at 2 years than the control group.  The primary outcome, BMI, did not differ significantly between the two groups at 2 years nor did change in body fat percentage.  (BMI did improve at 1 year, -0.57.)  In the small number of Hispanic participants (n=27 in experimental group), there was a significant change in BMI at both 1 and 2 years.

While consumption of sugar-sweetened beverages have been considered to be more fattening than solid foods because they do not lead to a sense of satiety, it appears that restriction of these beverages by itself will not make a major dent in the problem of obesity.

Related blog posts:

NAFLD Guidelines 2012

Treating diabetes with surgery

Lower leptin with physical activity

Staggering cost of obesity

Psychology of obesity and food addiction

Weight of the Nation

Cardiovascular disease for the entire family

TODAY is worrisome for a lot of tomorrows

How helpful are antioxidants for chronic pancreatitis pain?

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The ‘ANTICiPaTE’ study shows that antioxidants are not helpful in the typical patient with chronic pancreatitis (Gastroenterol 2012: 143: 655-63).  While chronic pancreatitis is a rare problem for the pediatric population, I was drawn to this study because I had to see what the acronym stood for: ANTI-oxidant therapy for painful Chronic Pancreatitis Therapy Evaluation.

In brief, this study was a double-blind placebo-controlled single-center randomized trila of Antox version 1.2 in patients with painful chronic pancreatitis.  The ingredients of this antioxidant included selenium, ascorbic acid, d-α-tocopherol and multiple secondary ingredients.  Antioxidant levels were measured as well and did increase on study medication.

Results: after 6 months, pain scores were reduced by 1.97 from baseline in placebo group and 2.33 in the antioxidant group.  The -0.36 difference was within the 95% confidence interval (-1.44 to 0.72).  Quality of life measures were similar as well.

The discussion points out that the largest randomized study (Bhardwaj et al) found that antioxidants were effective in relieving pain in chronic pancreatitis.  So why the discrepancy? Possible reasons:

  • 1. Different populations: Bhardwaj study had a younger population: 31 years compared with 50 years in current study
  • 2. Different etiologies: The Bhardwaj study had only 31% with alcoholic etiology for chronic pancreatitits compared with 72% in current study
  • 3. Comorbid conditions:  The Bhardwaj study had 28% smokers compared with 80% in current study
  • 4. Antioxidant constituents differed
  • 5. Chance

Take-home message: While there are notable differences between this study and the Bhardwaj study, the present study is more indicative of typical chronic pancreatitis patients in the U.S. and indicates that antioxidants are not effective in this population. For the pediatric population, the Bhardwaj study has more applicability; however, the present study diminishes optimism that antioxidants will be effective.

What are the alternatives? Both surgical and endoscopic treatments can be considered for chronic pancreatitis, though neither has consistently been effective at reducing pain.

Additional references:

  • -Bhardwaj P, et al. Gastroenterology 2009; 136: 149-59.  Antioxidants for chronic pancreatitis pain.  antioxidant included 600mcg selenium, 0.54g ascorbic acid
  • -Gastroenterol 2011; 141: 1690.  Surgical Rx outperformed medical Rx. n=79.  Only 5% of surgical pts needed more Rx.  47% of endoscopic pts eventually needed surgery, 68% of endoscopic pts had repeated procedures.
  • -NASPGHAN Postgraduate Course 2011: Exercise helpful in reducing pain/depression, coffee/green tea may help. Surgery (eg Puestow) -most commonly for pain —>75-80% good outcome.  Rarely Frey procedure & investigational pancreatectomy (harvesting islet cells) -n=24 in Minnesota. May benefit from dual sphincterotomy -bilary/pancreatitic (33% improve) but increased complications (pancreatitis, cholangitis, restenosis)
  • -Am J Gastro 2010 105: 1884.  –cleaning out ducts w ERCP-1/3rdimprove (some worsen)
  • -Clinical Gastro & Hep 2011; 9: 541.  steatorrhea (w pancreatitis) typical adult dosing of pancreatic enzymes: 40,000-50,000 IU lipase/meal & 1/2 dose for snacks.
  • -Gastroenterol 2011; 141: 536.  Pregabalin reduces pain in chronic pancreatitis -randomized control trial.

Related blog entries:

Does pancreas divisum cause pancreatitis?

Recurrent pancreatitis and genetic underpinnings

Pain changes brain

Picking the right diet for EoE

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A study from Philadelphia/CHOP offers more insight into food selection diets for eosinophilic esophagitis (EoE) (Spergel JM, et al, J Allergy Clin Immunol 2012; 130: 461-7) –thanks to Seth Marcus for forwarding this article to my attention.

For this study, the authors examined their database of 1187 patients.  While the data was collected prospectively, this was a retrospective study.  Of this 1187, the authors excluded patients with proton pump inhibitor-responsive EoE (n=191) along with patients with more extensive eosinophilic GI diseases (n=55).

Among the remaining 941, the male-to-female ratio was 2.8:1 and the average age was 6.4 years. Concurrent atopic disorders were common: 64% had rhinitis, 50% had asthma, and 24% had atopic dermatitis.  Only 18% had no atopic disorders.

The actual number for the study though was 319.  Among the 941 noted above, 148 were receiving medications (n=130 for topical steroids), and causative foods were not identified in 474.  In some of these patients, families were content to stick with a multiple food elimination without determining with certainty which foods were truly necessary.

In less than 5% of patients, a strict elemental diet was used.  In this group, the population was younger (average 2.8 years).  Biopsy improvement was noted in “upward of 98%.”

Key findings:

  • Elimination of foods based on combined skin prick tests (SPT)/atopy patch tests (APT) had an identical response to the six food group diet –53%.  The allergy testing group had less eliminated foods (average 3.2 foods) compared with 8 food groups in SFED.
  • Elimination of milk with SPT/APT testing resulted in 77% response.  Authors note that there was a “particularly high false-negative rate (34%)” with milk testing (SPT/APT).
  • Elimination of top 8 allergens: milk, soy, egg, wheat, and meats [chicken, turkey, pork, beef] had an identical response of 77%.
  • Elimination of milk, egg, and wheat had a success rate of 48%.  Milk only elimination had a 30% response rate.
  • Most common foods by biopsy: milk (35%), egg (13%), wheat (12%), soy (9%), corn (6%)
  • Most common foods by symptoms: milk (19%), egg (11%), wheat (9%), soy (10%), beef (8%)
  • IgE-mediated foods:  milk (10%), egg (17%), soy (4%), peanut (22%)

Additional useful information in the addendum of methods notes their technique for APT testing (which is not standardized across centers).  The authors use 2 g of dry foods in 2 mL of isotonic saline solution for most foods; for milk, they use 3 g of powdered milk with 1 mL of isotonic saline.  Then these mixtures are placed in aluminum cups (6- or 12-mm Finn chambers on Scanpore).  These cups are placed on patient’s backs and removed at 48 hours and read at 72 hours.

In addition, for each food, their tables list predictive values (positive predictive value, negative predictive value, sensitivity, and specificity) for SPTs, and for APTs.  Overall, the predictive values are quite variable and much different from the general population. For example, in the general population, the negative predictive value is essentially 100% for combination of SPT/APT.

Previous related blog entries:

Choosing topical therapy for EoE | gutsandgrowth

Guidelines for Eosinophilic Esophagitis | gutsandgrowth

Looking better or feeling better in EoE?

Look of improvement on an EoE diet

Eosinophilic Esophagitis -Six Food Group Diet

MicroRNA signature for eosinophilic esophagitis

The undiscovered country

Test your knowledge of Hepatitis E

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Typically, Hepatitis E virus (HEV) is not considered a frequent pathogen in the U.S.; however, anti-HEV antibody has been detected in 21% of U.S. in population-based surveys between 1988-94 and the prevalence increases with age. It has been associated with acute-on-chronic liver disease and has been overlooked in some individuals labeled as having drug-induced liver disease.  Thus, HEV is a significant cause of hepatitis and a useful review has been published (NEJM 2012; 367: 1237-44).  As such, see if your knowledge is up to the test.

Questions:

  • 1. True or False: Worldwide, HEV is probably the second most common form of acute hepatitis
  • 2. True or False: The autochthonous form is more common in developed countries and can be present in developing countries.  Extra credit, what does “autochthonous” mean?
  • 3. Best test to order to diagnose acute HEV?
  • 4. Animal(s) most likely associated with the autochthonous form of HEV: shellfish, swine,  or wild game
  • 5. True or False: there are 4 genotypes
  • 6. True or False: antibodies (IgG and IgM) appear at the time of clinical onset, just before elevations in serum aminotransferases and symptoms
  • 7. How long do these antibodies remain detectable?
  • 8. Which population is most prone to fulminant epidemic HEV?  Pregnant women, immunocompromised hosts, or infants
  • 9. Incubation period? a. 1-2 weeks    b. 3-8 weeks    c. 9-12 weeks
  • 10. Case fatality rate? a. 1%    b. 2-4%   c. 5%    d. 7-10%
  • 11. Name extrahepatic manifestations
  • 12. Best treatments for chronic HEV?

Answers:

  • 1. False, probably the most common cause of acute hepatitis
  • 2. True.  Autochthonous refers to locally-acquired or endemic HEV
  • 3. IgM for anti-HEV
  • 4, Swine, but the other two have been associated with cases as well
  • 5. True.  Types 1 and 2 are more common in developing countries and associated with waterborne outbreak/fecal-oral transmission
  • 6. True.
  • 7. IgM anti-HEV for only 3-12 months, IgG anti-HEV persists for “years, if not for life”
  • 8. Pregnant women. Nutritional and immunologic features may increase the risk of fulminant HEV in pregnant women.  Rates of HEV are lower in many immunocompromised groups.  Elderly patients are more at risk for mortality due to endemic form.
  • 9. b.
  • 10. c.
  • 11. Arthritis, pancreatitis, aplastic anemia, Guillain-Barre syndrome, Bell’s palsy, peripheral neuropathy, ataxia, and confusion
  • 12. Ribavirin alone for 12 weeks yields sustained virologic response in at least two-thirds; combination with peginterferon may increase the response.  Both are considered experimental at this time.

Previous quiz blog:

Test your knowledge of Clostridium difficile

Consensus guidelines after polypectomy

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The US Multi-Society Task Force (MSTF) on colorectal cancer has updated their recommendations and provided an update on the literature as well (Gastroenterol 2012; 143: 844-57).

Their recommendations are summarized in Table 1 of this article.  In brief, repeat colonoscopy is recommended at the following interval:

  • 10 years –If no polyps or small (<10 mm) hyperplastic polyps in rectum/sigmoid
  • 5-10 years –if 1-2 small (<10 mm) tubular adenomas
  • 3 years –if 3-10 tubular adenomas or if adenoma with high-grade dysplasia
  • ❤ years –if >10 adenomas
  • 1 year  –if serrated polyposis syndrome

Other important points include the recommendation of adopting split-dose bowel preparations and avoiding interval fecal testing within 5 years after colonoscopy.  If the bowel preparation is poor, the MSTF recommends that in most cases colonoscopy should be repeated within 1 year.  Newer techniques like chromoendoscopy, narrow band imaging, and magnification endoscopy have not been adequately studied to recommend them as part of  a surveillance strategy.

Related blog entries:

Colonoscopy, Split-dosing bowel preps, and Ottawa scores

Aspirin prophylaxis for colorectal cancer?

Additional references:

  • -Gastroenterol 2010; 138: 73, 27 (ed). Overutilization of colon screening in low risk situations and underutilization in high risk situations in clinical practice.
  • -Clin Gastro & Hep 2010; 8: 795. Juvenile Polyps. Describes frequent rate of recurrence (3 of 18 among single polyps) & 45% overall. n=257. 39% with at least 2 polyps. Among those with multiple polyps, 7 had mutations in either SMAD4 (mothers against decpentaplegic drosophilia), BMPR1A (bone morphogenetic protein), or PTEN (phosphatase & tensin homolog). Their recs: recheck with scope in 1-3 years depending on polyp burden and presence of dysplasia.
  • -Clin Gastro & Hep 2009; 7: 1217. Fewer polyps detected as day progresses at a VA hospital n=477 pts. 27% decline in polyp detection.
  • -NEJM 2009; 361: 1179. Review of screening for colorectal cancer.
  • -Gastroenterol 2009; 137: 792. Use of CT colonography -current appraisal.
  • -Ann Intern Med 2009; 150: 1-8. Says endoscopists miss most cancers on right side & colonosopy reduces cancer by ~60% primarily due to left-sided cancers.  Most, 73%, of colonoscopies not done by GI/colorectal surgery.
  • -Gastroenterol 2008; 134: 1570. Update recommendations from ACS, ACR, US Multi-society task force.
  • -Clin Gastro & Hep 2005; 3: 633.  Inherited polyposis syndromes & genetic testing.
  • -Clin Perspectives in Gastro 2002; 5: 329.  Polyp techniques & complications. If entrapped snare, consider cutting off snare handle & pulling on 1 wire. Alternative us to use snare as guidewire & push scope beyond wire. For large stalks, consider using snare as tourniquet for 5 min. Consider pure (or blended) coagulation at settings 20-30W.
    Injection of fluid into the submucosa beneath the polyp increases the distance between the polyp and the deeper layers of the colon. Using a sclerotherapy needle normal saline is injected at the edge of the polyp raising a bleb. No specific volume of normal saline is used. The objective is to raise a large bleb with marked elevation of the polyp. The snare is then placed around the base of the polyp and it can be removed with electrocautery. If bleeding is a consideration then a solution of epinephrine can be used at a 1:10,000 concentration. The advantage of cautery is that residual tissue is usually destroyed although this is usually not a consideration when removing juvenile polyps.Hot biopsy forceps are usually used to ablate diminutive polyps (< 5 mm in diameter). The coagulation current applied should be low. 10-15 watts applied for 1-2 seconds. The technique is generally safe but serious complications including bleeding or perforation have been reported.The cold snare technique is safe in small polyps. (< 5 mm) The rationale is that the vessels feeding the polyp are small and the risk of bleeding is low. The advantage is that without cautery there is not deep tissue damage. Submucosal injection may make the procedure safer.

RFA doesn’t always work for Barrett’s

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As noted previously in a related blog (Preventing Cancer in patients with Barrett’s Esophagus), Barrett’s esophagus (BE) is not a frequent issue in pediatric gastroenterology.  However, some esophageal problems that start in childhood can predispose to this condition later in life. Certainly, BE is a frequent clinical issue in adult gastroenterology.

Three articles in this month’s Gastroenterology provide some useful information.

  • Gastroenterology 2012; 143: 564-66
  • Gastroenterology 2012; 143: 567-75
  • Gastroenterology 2012; 143: 576-81

An editorial on these three articles is available on page 524.

The first reference describes three cases of high-grade dysplasia and adenocarcinoma that developed after ‘successful’ radiofrequency ablation (RFA).  Thus, the authors advocate continued surveillance following RFA and caution in using RFA to patients with low-risk BE.

The second reference describes an elaborate model to determine if RFA is cost-effective.  Based on their assumptions, “initial RFA might not be cost-effective for patients with BE without dysplasia.”   Though, the authors indicate that one of the cost savings was that RFA was more effective and less costly than endoscopic surveillance.  The authors acknowledge that their analysis is limited by assumptions and that the only alternative would be a large multicenter randomized trial with a long followup.

The third study examined 37 RFA patients.  22 were classified as complete responders and 15 were incomplete; complete responders had no intestinal metaplasia after fewer than 3 ablation sessions.  Risks for persistent intestinal metaplasia were uncontrolled weakly acidic reflux despite twice-daily PPI therapy, longer length of BE, and larger hiatal hernias.

Congenital hepatic fibrosis

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In a previous blog entry (Hepatic ciliopathies), I briefly discussed congenital hepatic fibrosis (CHF).  A more detailed review and handy reference: Srinath A, Shneider BL. JPGN 2012; 54: 580-87.

This invited review details information related to 1230 CHF patients from 155 articles (available at http://links.lww.com/MPG/A88).  Median and mean age of diagnosis were 2 and 11.2 years respectively.

Distribution of CHF cases/associated conditions: 118 isolated CHF, 788 autosomal recessive polycystic kidney disease, 315 with Caroli disease/syndrome, 9 with type V choledochal cyst

Clinical problems:

  • Sequelae of portal hypertension in 409 patients: 164 with varices, 74 with bleeding varicose, 81 underwent portosystemic shunting.  Portal hypertension itself was identified in 71-97% depending on the patient subset examined.
  • Cholangitis in 152 patients –often recurrent.  This was fatal in 3 of 23 children after renal transplantation.
  • Malignancy in 21 patients (2%). 19 were cholangiocarcinoma.  Of these cases, 10/19 had Caroli disease/syndrome, 7 had isolated CHF, 1 had ARPKD, and 1 had Type V choledochal cysts. Youngest patient with cholangiocarcinoma was 33 years, all other cases involved patients >40 years.

Transplantation: Isolated kidney 91 (95% in ARPKD), Isolated liver 173 (87% had Caroli), Combined 23.  Three renal patients subsequently had combined transplantation.

Other important points:

  • CHF is not ‘typically associated with progressive hepatic insufficiency.’ Only rarely is hepatic synthetic function compromised
  • Predisposition to cholangitis may affect transplantation decisions and timing

Increased bile acids in diarrhea-predominant IBS

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The role for bile acids in causation of irritable bowel gets a closer look in a recent publication (Clin Gastroenterol Hepatol 2012; 10: 1009-15).

This study randomly selected 52 participants (26 with diarrhea-predominant IBS, 26 with constipation predominant IBS) from a cohort of 700 IBS patients followed at the Mayo clinic along with 26 healthy volunteers.  The ages of the patients ranged from 29-51. Subsequently, these patients underwent additional testing following a 4-day high fat diet.  Of note, 5 of the IBS-D patients had a history of cholecystectomy compared with one patient in the other two groups.

In these patients, bile acid concentrations were measured in the stool and serum levels of 7α-hydroxy-4-cholesten-3-one (C4).In the IBS-D patients, serum levels of C4 were significantly higher than in the other two groups.  38% of the IBS-D group had elevated C4 levels; these elevated levels correlated with increased stool concentrations of bile acids.

The authors note that bile acid malabsorption has been identified frequently in patients with unexplained chronic diarrhea and that these patients often respond to bile acid sequestration (eg. cholestyramine or colesevelam).  Another interesting finding was that obesity was associated with elevated bile acid levels. Overall, the cohort with IBS-D had an average BMI of 29.5.

So, what conclusions can be drawn?

  • Serum C4 levels may be using in identifying patients with bile acid malabsorption
  • Bile acid sequestration agents may be worth a try in some cases of IBS-D and this study provides a rationale

Additional references:

-Alim Pharmacol Ther 2009; 30: 707-17.  Bile acid malabsorption in IBS-D.

Extended data with entecavir & annotated HBV management references

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Long-term data for entecavir continue to look good (Clin Gastroenterol Hepatol 2012; 10: 1047-1050).

With this study, the authors performed a post hoc analysis of 94 Asian patients with hepatitis B e antigen-positve (HBeAg+) nucleus(t)ice analogue-naive patients who received 5 years of entecavir therapy.  By five years, 66 patients remained in the study; of the other 28: 11 withdrew consent, 4 completed treatment, 5 died, 2 were lost to followup, 2 had minimal virologic response, and 4 had other reasons.

Results:

  • 63 of 66 (95%) patients who completed 5 years of therapy had HBV DNA < 300 copies/mL
  • 50 of 66 (76%) had normalized levels of alanine aminotransferase
  • 26 of 65 (40%) had HBeAg loss
  • 12 of 65 (18%) had HBeAg seroconversion
  • No resistance to entecavir was detected

Related blog entries:

References on Hepatitis B Management:

  • –Chronic Hepatitis B: Update_2009 AASLD Practice Guidelines
  • -Clin Gastroenterol Hepatol 2011; 9: 85. Mgt recommendations.
  • -Hepatology 2010; 52: 2192. Consensus guidelines suggest that IFN is treatment of choice in pediatric pts (<16yrs) due to resistance among nucleosides and lack of pediatric studies with these agents along with PEG-IFN. Does not recommend Rx for immune tolerant (NL ALT, HBeAg+, HBV >20K), inactive dz (NL ALT, HBeAg-Neg, HBV <2K), mild disease. Reactivation (HBeAg-Neg, HBV>2K IU/mL & +ALT1.5ULN or >60) & Immune active (+ALT1.5ULN or >60, HBeAg+, HBV >20K) can be treated if mod-severe dz.
  • -JPGN 2009; 48: 399-404. For children, IF +HBeAg/HBV DNA> 20,000 IU/mL & ALT>2 x ULN, Rx post 3months (sooner if decompensating). IF +HBeAg/HBV DNA> 20,000 IU/mL & ALT<2 x ULN or if inactive replication, then monitor. Consider: Follow yearly U/S, q6mo AFP.  IF HBV DNA <20K U/mL & NL ALT: no Rx, monitor q6-12mo. IF HBV DNA >20K U/mL & NL ALT, low rate of HBeAg conversion, young pts often immunotolerant, consider biopsy, esp if >35yrs.  IF HBV DNA >20K U/mL & incr ALT, then Rx options entecavir, tenofovir, PEG interferon alfa-2a preferred.
  • Hepatology 2009; 49: May 2009 supplement -Entirely on management of HBV: S1-S199. NIH Consensus conference. S8: “Reasonable to monitor this group ((younger than 40/HBeAg+) without therapy unless evidence of progressive liver disease is found” S10 Table 1 -Criteria for determining Rx. Generally not indicated: immune-tolerant phase (High HBV DNA but normal ALT or little activity on Bx).S119: “almost all of the oral agents are superior to interferon-based therapy in achieving other clinical endpoints…and in achieving biochemical and histological improvement…in addition, with longer use, oral agents can equal and exceed the level of pegIFN-associated HBeAg & HBsAg serologic responses w/o the need for injections, side effects…”
  • -Hepatology 2009; 49: 699. German Rx guidelines: IF HBV DNA+ & Cirrhosis –>Rx. IF HBV DNA >10 to 4th and any of the following: ALT >2X, F2 + inflammation, Risk HCC/extrahep dz—>Rx. If none of these reeval q6-12mo

Additional entecavir/tenofovir references:

  • -Gastroenterol 2011; 141: 1212. Entecavir effective as monotherapy post OLT.
  • -Hepatology 2010; 53: 763. No resistance with tenofovir over 2yrs. n=641 (HBe+ & HBe-neg)
  • -Gastroenterol 2011; 140: 132. n=365. Excellent efficacy of tenofovir over 3 yr Rx for HBV. 87% of HBeAg-neg with undetectable HBV & 74% of HBeAg-pos. 8% of HBeAg-pos lost HBsAg & 34% lost HBeAg.
  • -Hepatology 2009; 51: 73. n=131. Tenofovir Rx.
  • -Clin Gastroenterol Hepatol 2010; 9: 274. Use of entecavir (long term) reverses fibrosis in HBV
  • -Hepatology 2010; 52: 886. Long term entecavir Rx (>6yrs) with good efficacy & improved histology (96%), n=69.
  • -Hepatology 2009; 49: 1503. Long term entecavir Rx with LOW resistance. n=608 @ yr1, 108 @ yr5. Resistance ~1%
  • -Hepatology 2009; 50: 1064. Entecavir less effective in pts with combined LAM/ADV resistance.
  • -Hepatology 2008; 48: 99. Entecavir for lamivudine-refractory HBV thru 96 weeks. n=141 entecavir, n=145 lam. Entecavir fairly effective (81% had NL Alt, 10% HBeAg seroconversion) 6/77 in 2nd yr developed resistance much higher than those in studies who never rec’d lamivudine
  • -NEJM 2007; 356: 2614. Use entecavir with caution in pts coinfected w HIV -may select for resistant organisms in those not on fully sppressive antiretroviral regimens.
  • -NEJM 2006; 354: 1001, 1011, 1074. Hepatitis B patients: At 48 weeks, Entecavir-Rx’d HBeAg+ had 72% histologic response, 67% c undetectable HBV DNA, and 68% normalized ALT (n=314/314 entecavir/lamivudine pts). At 48 weeeks among HBeAG-neg, 90% in entecavir group (n=296 vs. 287 lamivudine pts) w/o detectable HBV DNA, 78% c Nl ALT, 70% c histologic improvement. Entecavir has caused cancer in mice.
  • -Hepatology 2006; 44: 1656. Entecavir had highly potent efficacy in reducing HBV DNA levels to <300 copies/mL. Study of 673 Rx’d pts. In HBeAg+, 69% were HBV DNA-neg at 48 weeks, & 82% at 96 weeks; in HBeAg-neg, 93% at 48 weeks & 96% at 96 weeks were HBV DNA neg. Low level of resistance due potent HBV DNA levels.

Life in the balance (book)

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While a recent blog (“There is More to Life Than Death”) referred to the complexity of  population-based medical decisions when relying solely on mortality, clearly mortality matters a lot.  In the same NEJM issue, an article highlights the difference that expanded Medicaid coverage has on mortality in adults (NEJM 2012; 367: 1025).

Traditionally, Medicaid has covered only low-income children, parents, pregnant women, and disabled persons.  In the past decade, several states expanded coverage to include nondisabled adults without dependent children.  This study examined these efforts in three states (New York, Arizona & Maine).  Then, effects on mortality were examined from 1997-2007 in these states as well as bordering states who did not expand coverage.  This time period allowed data to be analyzed five years prior to change and five years afterwards.

Findings:

  • By broadening eligibility requirements, there was a 25% increase in Medicaid coverage.
  • States with Medicaid expansions reduced all-cause mortality by 19.6 deaths per 100,000 adults; this was a relative reduction of 6.1%.
  • Mortality reductions were greatest for older adults (35-64), nonwhites, and residents of poorer counties.
  • The authors note that these changes do not prove causality.  However, there are implications for the affordable care act which allows expansion of eligibility up to 138% of the federal poverty level.

Despite apparent improvement in mortality, the cost, logistics and politics of expanding medical coverage remain unclear. In Georgia, the decisions on expanding medical coverage are quite controversial (see links below). My view: I think everyone in this country needs at least basic medical coverage.  This saves lives.

Deal rejects expansion of Medicaid | www.ajc.com

Expand Medicaid? – Blogs – Atlanta Journal-Constitution