The Year in Gastroenterology

MONTREAL, Dec. 29 -- Early reports about promising investigational compounds and new insights into the effect of diet on the gut buoyed gastroenterology news during the year.

But overshadowing the positive news were reports about emerging risks associated with a class of drugs that have transformed the every day practice of gastroenterology -- proton pump inhibitors.

The following summary reviews some of the highlights of the year in gastroenterology research. For fuller accounts, links to the individual articles published in MedPage Today have been provided.

Proton Pump Inhibitors

From the time that Prilosec (omeprazole), Prevacid (lansoprazole), Nexium (esomeprazole) and the other members of the class were approved as prescription drugs, to the OTC formulation of Prilosec, these drugs have been widely acclaimed for their efficacy in treating reflux disease.

That bright picture began to dim with early reports that proton pump inhibitors were linked to increased risk of Clostridium difficile infections.

Investigators from Royal Victoria Hospital in Montreal provided new evidence of a link between proton pump inhibitors and C. difficile in a case control study of 317 patients treated in the decade beginning in 1994.

The Canadian investigators, who reported their findings in September in the Canadian Medical Association Journal, said proton pump exposure was associated with a 3.5 fold increase in risk of C. difficile-associated disease.

By contrast, the Canadians said there was no increased risk for patients treated with H₂ -receptor agonists.

• Proton Pump Inhibitors Linked Anew to C. Difficile-Associated Disease

That disquieting report was followed by a study that linked long-term proton pump inhibitor use to increased risk of hip fracture.

In this study, which was reported in the Dec. 27 issue of the Journal of the American Medical Association, middle-age and older patients who used the heartburn drugs for more than a year had a 44% increase in risk of hip fracture, compared with controls who didn't use proton pump inhibitors.

Moreover, the risk was even greater -- a 2.6-fold increase in fracture risk -- for those who consumed about 1.75 times the recommended proton pump inhibitor dose for more than a year. The researchers from the University of Pennsylvania based their conclusions on analysis of medical records form 13,556 hip-fracture patients and 135,386 controls.

The Penn team recommends caution when prescribing proton pump inhibitors: start low, go slow. They also suggest having calcium onboard during proton pump inhibitor therapy.

• Proton Pump Inhibitors Linked to Fracture Risk

C. difficile

At the Infectious Diseases Society of America meeting there was encouraging news about an effective option for treating C. difficile.

In a randomized, double blind, head-to-head trial against Flagyl (metronidazole), which is the typical first-line therapy for C. difficile, vancomycin did significantly better in severe cases. The findings, according to Melinda Davis, M.D., of the University of Illinois, suggest that vancomycin should be the preferred first-line drug for treating severe cases.

• IDSA: Vancomycin Outdoes Flagyl in Severe C. difficile Diarrhea

Xifaxan

Another antibiotic, Xifaxan (rifaximin) that is approved for treatment of travelers' diarrhea, demonstrated efficacy for treatment of chronic abdominal bloating and flatulence, according to researchers from the University of Beirut who reported their findings in the American Journal of Gastroenterology.

In a double blind study of 124 patients with chronic bloating and flatulence -- including some with irritable bowel syndrome -- half were randomized to 400 mg of Xifaxan daily for 10 days and half to placebo. Forty-one percent of the Xifaxan patients reported symptom relief versus 23% of the placebo patients (P=0.03).

• Antibiotic Relieves Chronic Bloating and Flatulence

Yo-Yo Dieting

Yo-yo dieting, a term used to describe the cycle of taking weight off and putting it back on, which is familiar to many who are constantly fighting the battle of the bulge, increases the risk of gallstone disease in men, according to a National Cancer Institute study by investigators at the University of Kentucky and Harvard.

Analysis of data from the 51,529 men enrolled in the Health Professionals Follow-Up Study revealed that men who repeated go through weight loss-weight gain cycles increase their risk of gallstone disease by about 50% compared with men who maintain a stable weight.

Moreover, according to the results, reported in Archives of Internal Medicine, the greater the weight swings, the greater the risk. So men whose weight varied by less than 10 pounds increased their risk by about 10%, while those who regularly lost and then gained 50 pounds or more had a 51% increase in risk of gallstone disease.

• Gallstone Disease in Men Built on Weight Cycling

GERD and COPD

Acid reflux plus chronic obstructive pulmonary disease (COPD) is a dangerous combination, said Kenneth J. Vega, M.D., and colleagues from the University of Florida.

Writing in Chest, they reported that acid reflux can double COPD exacerbations compared with patients whose COPD is not complicated by reflux.

The exacerbations were associated with significantly more hospitalizations, more emergency room visits, more clinic visits, and more antibiotic use compared with COPD patients who were reflux-free.

• Acid Reflux Doubles COPD Exacerbations

NSAIDs and H. Pylori

As data accumulate about the link between nonsteroidal anti-inflammatory drugs (NSAIDs) and cardiovascular disease the FDA along with the American College of Cardiology and American Heart Association have issued recommendations about management of NSAIDs to limit cardiovascular risk.

The ACC-AHA and FDA all recommended low dose, short-term use for all NSAIDs --with the exception of aspirin.

In 2006, the American Gastroenterology Association weighed in with additional recommendations about NSAIDs, but this time with an eye toward limiting GI risk.

The main message from the AGA is that patients with a high risk for GI complications should be screened for Helicobacter pylori before initiating NSAID therapy.

• A Call to Test for H. Pylori Before Starting NSAIDs in High Risk Patients

Yreka

In a comparison trial reported at the American Society for the Study of Liver Diseases meeting, Tyzeka (telbivudine) was superior to Epivir (lamvudine) at reducing hepatitis B virus to undectable levels after two years.

That news came just a week after the FDA approved Tyzeka, a nucleoside inhibitor, as a once-daily antiviral therapy for chronic HBV infections.

The multicenter, international GLOBE trial randomized 1,367 adults to Tyzeka 600 mg/day or Epivir 100 mg/day.

• AASLD: Tyzeka Bests Epivir at HBV Control at Two Years

Chronic HCV

Also at AASLD, an investigational immunomodulator -- at Toll-like receptor 9 (TLR9) agonist -- demonstrated early antiviral activity in patients with difficult-to-treat chronic hepatitis C infections.

The compound, which is called Actilon (CPG 10101), was compared with pegylated interferon and Rebetol (ribavarin) and to a combination of Actilon plus Peg-IFN and Rebetol in patients with treatment refractory HCV genotype 1 who had relapsed after an initial course of Peg-IFN and Rebetol.

The patients in the Actilon plus Peg-IFN and Rebetol arm achieved significant reduction in HCV viral load.

• AASLD: Novel Drug Takes Toll on Hepatitis C

And at Digestive Disease Week, investigators from the University of Tuebingen in Germany reported that daily consensus interferon plus Rebetol was an effective treatment for patients who became refractory to Peg-IFN plus Rebetol.

The researchers said 70% of HCV patients treated with daily consensus interferon plus Rebetol achieved sustained viral response for 72 weeks.

But the researchers noted that the study was small -- just 81 patients -- so the findings require confirmation in a larger controlled trial.

• DDW: Relapsed HCV Patients Achieve Sustained Response with 72-Week Treatment

Also at DDW, 28 days of treatment with VX-950, an oral hepatitis C protease inhibitor, together with Pegasys (peginterferon alfa-2a), and Rebetol (ribavirin) achieved 100% rapid viral response in 12 treatment-nave HCV patients.

The 12 patients were continued on weight-based Rebetol therapy for 12 weeks. After 12 weeks, 11 of the 12 patients had undetectable virus, said Eric Lawitz, M.D., of the University of Texas at San Antonio in a late breaking clinical trials session at Digestive Disease Week here.

Dr. Lawitz said this study was "the third trial of the drug, but it is the first time [Rebetol] has been added, the first time we are evaluating 28-day treatment, and it is the first trial in the United States."

Moreover, Dr. Lawitz said that viral response is robust. "We are seeing a 2- to 3-log decline in the first two days of therapy," he said. "Two patients reached "undetectable levels of HCV RNA within eight days." Undetectable HCV RNA was defined as viral load less than 10 IU/mL.

• DDW: Novel HCV Protease Inhibitor Promising in Early Trial

Esophageal Cancer

The high-carbohydrate, low-carbohydrate diet debate continued throughout 2006 and at the American College of Gastroenterology meeting there was a report that a diet heavy in carbohydrates might tip the scales in favor of a cascade of factors that lead to increased risk of esophageal cancer.

Investigators from Case Western Reserved University in Cleveland said analysis of Surveillance, Epidemiology, and End Results (SEER) data form 1973 through 2001 suggests that esophageal cancer increased as carb consumption increased.

• ACG: Carb-Heavy Diet Linked to Esophageal Cancer

Constipation

In another report from ACG, Mayo Clinic researchers reported that chronic constipation may signal a 20% rise in the 10-year risk of death.

The analysis, which was based on data from some 4,000 residents of Olmstead County, Minnesota, determined that the estimated 10-year survival rate from 1990 to 2000 for those with chronic constipation was 73%, compared with 85% for non-constipated persons (P