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What's new in gastroenterology and hepatology

Disclosures: Peter A L Bonis, MD Employee of UpToDate, Inc. Anne C Travis, MD, MSc, FACG, AGAF Employee of UpToDate, Inc. Equity Ownership/Stock Options: Proctor & Gamble [Peptic ulcer disease, esophageal reflux (omeprazole)]. Shilpa Grover, MD, MPH Employee of UpToDate, Inc.

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All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Nov 2014. | This topic last updated: Dec 16, 2014.

The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.

COLORECTAL CANCER

Colorectal cancer mortality after adenoma resection (August 2014)

There are limited data regarding the incidence and mortality from colorectal cancer in patients who have had colorectal adenomas resected. In a study that included approximately 40,000 patients from a Norwegian population based registry who had undergone resection of a colorectal adenoma, 1273 patients were diagnosed with colorectal cancer during a median follow up of nearly eight years [1]. As compared with the general population, individuals who had undergone resection of one tubular adenoma of any size had a lower colorectal cancer mortality, while those with two or more adenomas, high grade dysplasia, or villous histology had a higher colorectal cancer mortality. Studies are needed to determine if intensive colorectal cancer surveillance reduces colorectal cancer mortality among individuals with high-risk adenomas. (See "Approach to the patient with colonic polyps", section on 'Surveillance'.)

Colorectal cancer screening in older adults who have never been screened (July 2014)

For most older adults, it is reasonable to stop screening for colorectal cancer (CRC) at age 75 years, or 85 years at the latest. However, for older adults who have never been screened for CRC (23 percent of US elderly individuals), one-time screening appears to be cost-effective up to age 86 years, based on results of a modeling study [2]. In this simulation study, assuming a willingness to pay $100,000 per quality-adjusted life-year gained, colonoscopy was cost-effective to age 83 years, sigmoidoscopy to 84 years, and fecal immunochemistry testing to 86 years for patients without comorbidity and at average risk for CRC. Colonoscopy was the most effective, and most expensive, strategy for one-time screening. (See "Screening for colorectal cancer: Strategies in patients at average risk", section on 'Older adults with no prior screening'.)

ENDOSCOPY

Infection associated with contaminated endoscopes (October 2014)

In January 2014, the Centers for Disease Control and Prevention (CDC) reported that since January 2013, 69 cases of New Delhi metallo-beta-lactamase (NDM)-producing carbapenem-resistant Enterobacteriaceae (CRE) had been identified in the United States, 44 of which were from northeastern Illinois [3]. Further investigation identified 39 cases from one hospital [4]. The source of infection was subsequently traced to the elevator channel of a single duodenoscope (the endoscopes used for endoscopic retrograde cholangiopancreatography [ERCP]). No lapses in the cleaning protocol were identified. It is theorized that the complex design of the elevator mechanism makes it more difficult to clean than other parts of endoscopes [4,5]. After changing duodenoscope reprocessing from high-level disinfection to gas sterilization with ethylene oxide, no new cases have been identified. Duodenoscopes should be considered as possible sources for CRE outbreaks in healthcare facilities. (See "Endoscope disinfection", section on 'Carbapenem-resistant Enterobacteriaceae'.)

Preprocedure testing for endoscopic procedures (July 2014)

The American Society for Gastrointestinal Endoscopy has released guidelines regarding testing prior to endoscopic procedures [6]. The guidelines recommend that patients not undergo routine preprocedure laboratory testing, chest radiography, or electrocardiography. Instead, preprocedure testing should be obtained selectively based upon the patient’s medical history, physical examination findings, and procedural risk factors. (See "Overview of colonoscopy in adults", section on 'Preprocedure testing'.)

ESOPHAGEAL AND GASTRIC DISEASE

Lower risk of fatal bleeding with target specific oral anticoagulants versus warfarin (November 2014)

All anticoagulants carry a risk of bleeding, and the lack of an antidote for direct factor Xa inhibitors (rivaroxaban, apixaban, edoxaban) and the direct thrombin inhibitor dabigatran increases concerns about this risk. Reassuringly, a meta-analysis of 12 randomized trials in patients with atrial fibrillation or venous thromboembolism that compared bleeding risk with these agents versus vitamin K antagonists found lower rates of fatal bleeding, major bleeding, and intracranial bleeding with the direct factor Xa and direct thrombin inhibitors [7]. Individual patient factors continue to play a role in anticoagulant choice and the development of reversal agents for the factor Xa and thrombin inhibitors is underway. (See "Management of bleeding in patients receiving target-specific oral anticoagulants", section on 'Risk of bleeding'.)

Intermittent dosing of proton pump inhibitors for peptic ulcer bleeding (October 2014)

Treatment with proton pump inhibitors (PPIs) leads to elevation of gastric pH levels, which stabilizes blood clots and improves clinical outcomes. As a result, PPIs are recommended for all patients with peptic ulcer bleeding. High-dose continuous infusions of intravenous (IV) PPIs have traditionally been recommended for patients presenting with upper gastrointestinal bleeding. However, several meta-analyses of randomized trials have failed to show superior outcomes with high-dose continuous IV proton pump administration compared with intermittent dosing (eg, 40 mg IV twice daily). In addition, intermittent dosing could lead to decreased resource utilization and cost. In the most recent meta-analysis, intermittent dosing was not inferior to high-dose continuous infusions with regard to rebleeding, mortality, need for surgery or repeat intervention, or the need for urgent intervention in patients with peptic ulcers with high-risk stigmata (active bleeding, adherent clot, or a visible vessel) [8]. There was also a trend toward a decreased risk of rebleeding with intermittent dosing. Based on this cumulative evidence, for patients presenting with upper gastrointestinal bleeding, we now recommend treatment with IV pantoprazole, esomeprazol, or omeprazole (where available) at a dose of 40 mg twice daily rather than a high-dose continuous infusion. (See "Overview of the treatment of bleeding peptic ulcers", section on 'Summary and recommendations' and "Overview of the treatment of bleeding peptic ulcers", section on 'Continuous versus intermittent dosing'.)

HEPATOLOGY

Increasing prevalence of nonalcoholic fatty liver disease (December 2014)

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder in Western industrialized countries. In the United States, the prevalence of NAFLD has been increasing over time. Between 1988 and 1994, the estimated prevalence using the National Health and Nutrition Examination Survey (NHANES) was 19 percent. The prevalence increased to 30 percent between 2011 and 2012 based on a more recent study using NHANES [9]. (See "Epidemiology, clinical features, and diagnosis of nonalcoholic fatty liver disease in adults", section on 'Prevalence'.)

Surrogate endpoints predict survival in primary biliary cirrhosis (November 2014)

Surrogate outcomes, such as alkaline phosphatase and bilirubin levels, are often used as endpoints in studies examining treatments for primary biliary cirrhosis (PBC). However, whether these surrogates predict patient-important outcomes was unclear. In a meta-analysis of 15 studies of patients with PBC, increasing alkaline phosphatase and bilirubin levels were associated with decreased transplant-free survival [10]. This meta-analysis supports using these surrogate endpoints in PBC treatment trials. (See "Clinical manifestations, diagnosis, and natural history of primary biliary cirrhosis".)

Direct-acting antiviral agents for post-transplantation hepatitis C recurrence (November 2014)

Recurrence of hepatitis C virus (HCV) following liver transplantation occurs in more than 95 percent of patients who fail to have the virus eradicated prior to transplantation. Current treatment regimens using direct-acting antiviral agents such as sofosbuvir and simeprevir are based largely on studies in patients with HCV who have not undergone liver transplantation. Treatment of patients with HCV recurrence after liver transplantation with direct-acting antiviral agents was recently examined in a study with 34 patients [11]. The patients were given ombitasvir (an NS5A inhibitor), ritonavir-boosted paritaprevir (a protease inhibitor), dasabuvir (a nonnucleoside NS5B polymerase inhibitor), and ribavirin for 24 weeks. A sustained virologic response at 24 weeks was achieved by 97 percent of patients, with no episodes of graft rejection. This study supports the use of direct-acting antiviral agents in patients with HCV recurrence following liver transplantation. (See "Liver transplantation for hepatitis C virus infection", section on 'Other regimens'.)

Prophylactic antibiotics do not benefit patients with acute liver failure (October 2014)

The role of prophylactic antibiotics in the treatment of patients with acute liver failure is controversial. In a retrospective study of 1551 patients with acute liver failure, antimicrobial prophylaxis did not reduce the incidence of bloodstream infection or mortality [12]. Our approach to antibiotic prophylaxis is to not give patients prophylactic antibiotics, but instead give antibiotics only if there is evidence of active infection, positive surveillance culture results, or clinical deterioration. (See "Acute liver failure in adults: Management and prognosis", section on 'Infection surveillance and prevention'.)

Ledipasvir-sofosbuvir for genotype 1 chronic hepatitis C infection (December 2013, MODIFIED October 2014)

Interferon-free options for chronic genotype 1 hepatitis C virus (HCV) infection are increasing. A once-daily combination pill of two direct-acting antiviral agents, ledipasvir and sofosbuvir, is becoming available in the United States and elsewhere. In several large open-label trials, ledipasvir-sofosbuvir achieved sustained virologic response (SVR) rates exceeding 90 percent in genotype 1 infected patients regardless of treatment history or presence of cirrhosis [13-15]. For all patients with chronic genotype 1 HCV infection, we favor the regimen of ledipasvir-sofosbuvir because of its efficacy, its favorable adverse effect profile, its ease of administration, and extensive data to support its use. For treatment-naïve patients, treatment duration is eight weeks for those without cirrhosis and a viral level <6 million international units/mL, and 12 weeks for those with cirrhosis or a higher viral level. For treatment-experienced patients, treatment duration is 12 weeks for those without cirrhosis and 24 weeks for those with cirrhosis. (See "Treatment regimens for chronic hepatitis C virus genotype 1", section on 'Selection of treatment regimens'.)

Granulocyte colony-stimulating factor for severe alcoholic hepatitis (September 2014)

Granulocyte colony-stimulating factor (GCSF) has been proposed as a possible treatment for severe alcoholic hepatitis because it may mobilize bone marrow-derived stem cells and promote hepatic regeneration. In a randomized, nonblinded trial, 46 patients with severe alcoholic hepatitis were assigned to receive standard medical care (pentoxifylline with supportive care) plus GCSF or standard medical care alone [16]. Survival at 90 days was higher in the patients who received GCSF than in those who did not (78 versus 30 percent). However, the survival rate in patients who received standard medical care alone was lower than has been seen in other trials of pentoxifylline, so the role of GCSF in the treatment of severe alcoholic hepatitis remains unclear. (See "Alcoholic hepatitis: Natural history and management", section on 'Possibly effective treatments'.)

Risk of perinatal transmission of HBV in the United States (June 2014)

Administration of hepatitis B virus (HBV) vaccination and hepatitis B immune globulin (HBIG) to newborns of women with chronic HBV infection significantly reduces the risk of perinatal HBV transmission but does not eradicate it. In an observational study of over 4000 infants born to HBV-infected mothers in the United States between 1997 and 2010, over 95 percent received HBV vaccination and HBIG [17]. Perinatal transmission occurred in 3.40 percent of births to hepatitis B e antigen (HBeAg) positive mothers and 0.04 percent of births to HBeAg negative mothers. Among women whose HBV DNA results and HBeAg status were known, no HBV transmission occurred with a viral load less than 5 x107 IU/mL, regardless of the HBeAg status. (See "Hepatitis B and pregnancy", section on 'HBV DNA level'.)

Screening for Hepatitis B virus infection in the United States (June 2014)

Infection with Hepatitis B virus (HBV) can lead to chronic liver disease and is preventable with vaccination. The US Preventive Services Task Force (USPSTF) has updated its statement on screening for HBV infection in nonpregnant adolescents and adults to recommend that individuals at high-risk for HBV infection be screened if they have not been vaccinated or if they were vaccinated without prior screening [18]. High-risk populations include persons born in regions with a prevalence of HBV ≥2 percent, US–born persons whose parents were born in regions with a prevalence ≥8 percent, injection drug users, men who have sex with men, household contacts of persons with HBV infection, and individuals with HIV infection. Existing guidelines from the Centers for Disease Control and Prevention and the American Association for the Study of Liver Disease also support screening of high-risk individuals in the US. (See "Diagnosis of hepatitis B virus infection", section on 'Who should be tested or screened'.)

Glucocorticoids after hepatoportoenterostomy for biliary atresia (June 2014)

New clinical evidence demonstrates that glucocorticoids are not useful in the treatment of biliary atresia after hepatoportoenterostomy (Kasai procedure). In a multicenter randomized trial that included 140 infants with biliary atresia, compared with placebo, glucocorticoid treatment improved neither bile drainage six months postoperatively nor survival with the native liver at two years of age [19]. Moreover, infants treated with glucocorticoids had earlier onset of serious adverse events. This trial resolves questions about the utility of glucocorticoid treatment that were raised by previous retrospective or under-powered studies, which had conflicting results. (See "Biliary atresia", section on 'Glucocorticoids'.)

PANCREATIC AND BILIARY DISEASE

Enteral feeding in acute pancreatitis (November 2014)

Some nutritional guidelines have suggested that enteral nutrition be initiated early (within 24 to 48 hours) in all patients with severe acute pancreatitis to decrease the risk of major infection, although evidence to support this recommendation is lacking. In a randomized trial, 208 patients with severe acute pancreatitis were assigned to early nasoenteric tube feeding (within 24 hours of randomization) or an oral diet at 72 hours with on-demand nasoenteric tube feeding if an oral diet was not tolerated at 96 hours [20]. There was no difference in the primary endpoint (composite of major infection or death at six months) between patients who received early versus on-demand nasoenteric tube feeding. In the on-demand group, approximately one-third of patients required nasoenteric tube feeding. This study supports our preference to initiate enteral tube feeding in patients who are unable to tolerate an oral diet within 96 hours. (See "Management of acute pancreatitis", section on 'Enteral'.)

Imaging prior to laparoscopic cholecystectomy (October 2014)

In patients who need to undergo cholecystectomy but are at intermediate-risk for having a common bile duct stone, imaging (endoscopic ultrasound [EUS] or magnetic resonance cholangiopancreatography) is typically obtained prior to surgery to exclude a stone. An alternative is to proceed to laparoscopic cholecystectomy with intraoperative cholangiography. This approach was examined in a randomized trial with 100 patients at intermediate risk of having a common bile duct stone [21]. Patients were assigned to either laparoscopic cholecystectomy with intraoperative cholangiography or initial EUS (followed by ERCP if positive) and subsequent laparoscopic cholecystectomy. Patients who proceeded directly to surgery had a shorter median length of stay, without a difference in complication rates or mortality. If a surgeon experienced with intraoperative cholangiography is available, proceeding directly to laparoscopic cholecystectomy is a reasonable alternative to obtaining preoperative imaging. (See "Choledocholithiasis: Clinical manifestations, diagnosis, and management", section on 'Intermediate-risk patients'.)

Postoperative antibiotics following cholecystectomy (October 2014)

Antibiotics are often given to patients with acute cholecystitis to prevent infectious complications, but few studies are available to guide the use of postoperative antibiotics following cholecystectomy in this setting. In a multicenter trial that randomly assigned 414 patients with mild or moderate calculous cholecystitis to continue their preoperative antibiotic regimen or to receive no antibiotics following cholecystectomy, there were no differences in postoperative infection rates [22]. The results of this trial support the common practice of discontinuing antibiotics after cholecystectomy in patients with uncomplicated cholecystitis. Clinical judgment should dictate antibiotic management in complicated cases. (See "Treatment of acute calculous cholecystitis", section on 'Antibiotics'.)

SMALL BOWEL AND COLONIC DISEASE

Sleep duration and inflammatory bowel disease (December 2014)

Sleep deprivation has been associated with the production of inflammatory cytokines. A prospective cohort study evaluated sleep duration in more than 150,000 women and the incidence of inflammatory bowel disease [23]. During a follow-up of nearly 3 million person-years, there were 91 incident cases of Crohn disease and 230 cases of ulcerative colitis. As compared with women with reported usual sleep durations of 7 to 8 hours/day, women with reported sleep duration of <6 or >9 hours/day had a higher risk of ulcerative colitis. The investigators hypothesized that longer duration of sleep may be associated with poor sleep quality or fragmented sleep, which, like sleep deprivation, can promote a proinflammatory state. In contrast, sleep duration did not modify the risk of Crohn disease. Further studies are needed to explore the mechanisms by which sleep may influence intestinal inflammation and if modification of sleep duration can decrease the risk of inflammatory bowel disease. (See "Definition, epidemiology, and risk factors in inflammatory bowel disease", section on 'Sleep duration'.)

Posttreatment surveillance colonoscopy in older adults (August 2014)

Expert guidelines for surveillance of patients with treated colorectal cancer (CRC) or adenomatous polyps do not specifically address when, if ever, surveillance endoscopy should be stopped. In a retrospective cohort study of more than 25,000 patients ≥50 years of age (nearly 5,000 aged 75 or older) undergoing surveillance colonoscopy at a single integrated California health system for a history of CRC or adenomatous polyps, older age was independently associated with a higher risk of post-procedure hospitalization, as was the presence of a Charlson comorbidity score of 2 or higher (table 1) [24]. The risk of post-procedure hospitalization and the impact of comorbidity should be taken into account when assessing the relative risks and benefits of periodic surveillance colonoscopy in patients with advanced age or comorbidities and a history of treated CRC or colonic adenoma. (See "Surveillance after colorectal cancer resection", section on 'Guidelines from major groups' and "Approach to the patient with colonic polyps", section on 'Surveillance'.)

Lack of increased cancer risk from TNF inhibitors in patients with inflammatory bowel disease (June 2014)

There is some uncertainty whether the use of tumor necrosis factor (TNF) inhibitors increases the risk of cancer, particularly in patients with rheumatoid arthritis. Less information has been available regarding such risk in patients with other disorders. The cancer risk of TNF inhibitors in patients with inflammatory bowel disease (IBD) was examined in a study using a nationwide registry in Denmark, involving over 56,000 patients with IBD, of whom about 4600 were exposed to TNF inhibitor therapy with median follow-up of 3.7 years [25]. After adjustment for multiple potential confounders, there was no evidence that patients exposed to TNF inhibitors experienced an increased risk for cancer compared with unexposed patients. There was also no evidence of increased risk with cumulative dose, although risk with a greater duration of exposure or follow-up than in the study could not be excluded. (See "Tumor necrosis factor-alpha inhibitors: Risk of malignancy", section on 'Evidence of no increased long-term risk'.)

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REFERENCES

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