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What's new in gastroenterology and hepatology
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What's new in gastroenterology and hepatology
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Nov 2017. | This topic last updated: Dec 14, 2017.

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

Duration of benefit of one-time screening sigmoidoscopy (June 2017)

Sigmoidoscopy is one of several methods to screen for colorectal cancer in average-risk persons. In extended follow-up of a randomized trial, a one-time screening flexible sigmoidoscopy for people aged 55 to 64 years was associated with reduced colorectal cancer incidence and mortality even 17 years after the initial screening exam [1]. Similar benefits had been seen at 11-year follow-up. Although these findings support one-time flexible sigmoidoscopy as a potential screening method, most groups that include sigmoidoscopy as a screening option currently recommend repeated testing, although the optimal repeat interval is not known. In agreement with recommendations of the US Preventive Services Task Force, when flexible sigmoidoscopy is chosen as a screening modality, we offer flexible sigmoidoscopy alone every five years or flexible sigmoidoscopy every 10 years plus fecal immunochemical testing (FIT) every year. (See "Tests for screening for colorectal cancer: Stool tests, radiologic imaging and endoscopy", section on 'Evidence of effectiveness' and "Screening for colorectal cancer: Strategies in patients at average risk".)

ENDOSCOPY

Reprocessing methods for duodenoscopes (November 2017)

Infection can be transmitted through duodenoscopes despite adherence to reprocessing protocols. The US Food and Drug Administration has suggested additional reprocessing measures to reduce that risk, but data informing the optimal method are limited. In a trial that analyzed over 500 cultures taken from the working channel and elevator mechanism of reprocessed duodenoscopes, there were no differences in bacterial growth rates after single high-level disinfection, double high-level disinfection, or single high-level disinfection followed by ethylene oxide gas sterilization [2]. More study is needed to identify the most effective protocol for reprocessing duodenoscopes. (See "Endoscope disinfection", section on 'Special considerations for reprocessing of duodenoscopes'.)

Oral fluid intake before anesthesia (August 2017)

Oral intake is generally restricted for two hours before anesthesia, but the volume of clear liquids that should be allowed before this deadline is unclear. In a study of patients who drank ≥2 liters of bowel preparation solution before colonoscopy, no difference in gastric residual volume or gastric pH was observed between those who finished the solution as late as three hours prior to the procedure versus those who finished it the night before [3]. These data provide support for allowing patients free access to clear liquids until two hours prior to anesthesia and are particularly relevant to enhanced recovery after surgery protocols, which may include ingestion of 300 to 400 mL of carbohydrate drinks up to two hours prior to surgery. (See "Preoperative fasting guidelines", section on 'Clear liquids'.)

ESOPHAGEAL AND GASTRIC DISEASE

Revised recommendations for endoscopy in the evaluation of dyspepsia (November 2017)

The American College of Gastroenterology (ACG) and Canadian Association of Gastroenterology (CAG) have published guidelines on the evaluation and management of dyspepsia [4]. The recommended age threshold for routine upper endoscopy in patients with dyspepsia, to exclude upper gastrointestinal neoplasia, has been raised to ≥60 years, in contrast to earlier guidelines advising ≥55 years. The new guidelines also recommend that patients <60 years with dyspepsia be tested for Helicobacter pylori and treated if positive. For patients <60 years, upper endoscopy is reserved for those with significant weight loss, overt gastrointestinal bleeding, more than one alarm feature (table 1), or rapid progression of one or more alarm features. The rationale for these revised recommendations is the low risk of gastric cancer in younger patients, the low positive predictive value of any single alarm feature in detecting gastrointestinal neoplasia, and the inherent risk and cost of performing upper endoscopy. Our management approach is generally consistent with these guidelines (algorithm 1). (See "Approach to the adult with dyspepsia", section on 'Diagnostic strategies and initial management'.)

Recurrence of acid reflux after laparoscopic anti-reflux surgery (October 2017)

Although over 90 percent of patients are satisfied with the results of their anti-reflux surgery, criteria defining treatment success or failure vary among studies. In a population-based study from Sweden including over 2600 patients who underwent laparoscopic anti-reflux surgery, 18 percent developed recurrent reflux necessitating either long-term use of anti-reflux medications (393 patients) or repeat anti-reflux surgery (77 patients) at median follow-up of 5.6 years [5]. Risk factors for recurrence included female sex, older age, and comorbidity. (See "Surgical management of gastroesophageal reflux in adults", section on 'Long-term efficacy'.)

Four-food elimination diet for eosinophilic esophagitis (July 2017)

The traditional six-food (cow's milk, hen's egg, soy, wheat, peanut/tree nuts, and fish/shellfish) elimination diet for eosinophilic esophagitis (EoE) results in resolution of EoE in approximately three-quarters of children but is challenging and can have negative nutritional consequences. In a prospective study of four-food elimination (milk, soy, egg, wheat) in 78 children with EoE, histologic remission was achieved in 64 percent, with decreased symptoms in 91 percent [6]. Thus, we now suggest either the four-food or six-food empiric elimination diet for most patients who opt for dietary management of EoE. (See "Dietary management of eosinophilic esophagitis", section on 'Elimination diets'.)

PPI use and mortality (July 2017)

It is unclear if proton pump inhibitor (PPI) use is associated with an increase in risk of death. In an observational cohort study, the incident death rate among 275,977 new PPI users was higher than among 73,335 new histamine-2 receptor antagonist (H2RA) users over a median follow-up of 5.7 years (4.5 versus 3.3 per 100 person-years) [7]. After adjusting for potential confounders, PPI use was associated with increased all-cause mortality compared with H2RA use (HR 1.25); the risk of death increased with the duration of PPI use. Limitations of the study include its generalizability as the study cohort primarily consisted of older white males and lack of data on the cause of mortality. The underlying basis for this apparent increased risk of death with PPI use is not known, and further studies are needed to evaluate whether the association is due to unmeasured confounding. However, we continue to recommend that PPIs be prescribed at the lowest dose for the shortest duration appropriate for the condition being treated. (See "Proton pump inhibitors: Overview of use and adverse effects in the treatment of acid related disorders", section on 'Mortality'.)

HEPATOLOGY

New adjuvanted recombinant hepatitis B vaccine (November 2017)

Hepatitis B vaccination is the best way to prevent hepatitis B virus transmission. Available nonadjuvanted recombinant vaccines are effective and extremely safe, although they require three doses and 5 to 10 percent of patients do not respond. In November 2017, the US Food and Drug Administration granted conditional approval of a new adjuvanted vaccine (HEPLISAV-B) for adults 18 years and older [8]. This vaccine, given in two doses, appears more immunogenic than the nonadjuvanted vaccines and is generally well tolerated. However, there are ongoing safety concerns regarding a potentially increased risk of acute myocardial infarction and immune mediated disorders, which will be further evaluated in a phase 4 study. The optimal use of this vaccine is thus still to be determined. (See "Hepatitis B virus vaccination", section on 'Single antigen vaccines'.)

Increase in immune globulin dose for prevention of hepatitis A (September 2017)

Intramuscular immune globulin (IG) is protective against hepatitis A virus (HAV) infection and is used for pre- and postexposure prophylaxis instead of vaccination in certain situations. The level of neutralizing anti-HAV antibodies in GamaSTAN, the intramuscular IG product available in the United States, appears suboptimal, reflecting low prevalence of prior HAV infection among plasma donors [9]. Therefore, increased dosing for GamaSTAN is now recommended when used for HAV prevention [10,11]. The new dose for preexposure prophylaxis is 0.1 mL/kg (for anticipated risk of exposure up to one month) or 0.2 mL/kg (for anticipated risk of exposure up to two months, with repeat dosing every two months for longer anticipated risk). The new dose for postexposure prophylaxis is 0.1 mL/kg. (See "Hepatitis A virus infection: Prevention", section on 'Passive immunization'.)

HEV infection in Europe and outbreaks in Africa (August 2017)

Hepatitis E virus (HEV) infection has a global distribution and is most commonly transmitted through contaminated food or water. In July 2017, World Health Organization reported an outbreak of HEV in Nigeria, where a humanitarian crisis has resulted in poor access to safe water and health services [12]. An earlier outbreak in nearby Niger had been reported in May 2017. In a separate 2017 surveillance analysis, the European Centre for Disease Prevention reported an increase in the number of confirmed HEV cases in Europe from 514 cases in 2005 to 5617 cases in 2015 [13]. It is unclear if this represents a true rise in HEV incidence in Europe or an increase in case detection due to growing awareness and testing for HEV. (See "Hepatitis E virus infection", section on 'Epidemiology'.)

Anticoagulant therapy in patients with cirrhosis and portal vein thrombosis (August 2017)

Anticoagulant therapy may be beneficial for patients with cirrhosis and portal vein thrombosis. In a meta-analysis of eight studies including over 350 such patients, patients treated with anticoagulants (ie, low molecular-weight heparin or warfarin) had higher rates of either partial or complete recanalization compared with untreated patients (71 versus 42 percent) [14]. In six studies, the overall rate of bleeding was similar with or without anticoagulation (11 percent in both groups). We individualize the decision to anticoagulate in this setting, taking into account several factors including the risk of bleeding, the risk of further thrombosis, and whether the patient is awaiting liver transplantation. (See "Chronic portal vein thrombosis in adults: Clinical manifestations, diagnosis, and management", section on 'Cirrhotic patients'.)

Novel HBV mutation associated with tenofovir and entecavir failure (August 2017)

For patients with chronic hepatitis B virus (HBV) infection, tenofovir is one of the preferred antiviral agents. To date, no signature tenofovir-resistance mutations have been identified in HBV. However, in a report of two HBV-infected patients with persistent viremia despite therapy with tenofovir and entecavir, molecular analyses identified a shared distinct mutation, rtS78T/sC69, which was associated with decreased susceptibility to both tenofovir and entecavir in vitro [15]. The prevalence and significance of this mutation remains to be determined. (See "Tenofovir and adefovir for the treatment of chronic HBV infection", section on 'Risk of resistance'.)

Glecaprevir-pibrentasvir and sofosbuvir-velpatasvir-voxilaprevir for chronic HCV infection (August 2017)

Treatment options for patients with chronic hepatitis C virus (HCV) continue to grow. Two new combination therapies, glecaprevir-pibrentasvir and sofosbuvir-velpatasvir-voxilaprevir, were recently approved by the Food and Drug Administration in the United States and are expected to be approved in Europe this year. Glecaprevir-pibrentasvir is highly effective for patients with genotypes 1 through 6 infection, offers the possibility of an eight-week regimen for most patients without cirrhosis, and can be used in patients with renal impairment (including those on dialysis) [16-19]. It is now one of our preferred regimens for all genotypes; regimen duration depends on the genotype, the presence of cirrhosis, and the treatment history (algorithm 2 and algorithm 3 and algorithm 4 and algorithm 5). Sofosbuvir-velpatasvir-voxilaprevir is highly effective in patients with genotypes 1 through 6 infection who have failed a prior direct acting antiviral (DAA) regimen and is now the main treatment option for those who have failed an NS5A inhibitor-containing regimen [20]. Like other contemporary DAA regimens, these new combinations are well tolerated, with common but mild side effects. (See "Treatment regimens for chronic hepatitis C virus genotype 1 infection in adults", section on 'Selection of treatment regimens' and "Treatment regimens for chronic hepatitis C virus genotypes 2 and 3 infection in adults", section on 'Selection of treatment regimen' and "Treatment regimens for chronic hepatitis C virus genotypes 4, 5, and 6 infection in adults", section on 'Selection of treatment regimens'.)

PANCREATIC AND BILIARY DISEASE

Comparison of minimally invasive pancreatic debridement strategies for infected necrosis (November 2017)

Acute pancreatitis can lead to necrosis of the pancreatic parenchyma. Infected necrosis requires debridement, which traditionally has been performed with open surgery. Now, a Dutch multicenter randomized trial has evaluated two minimally invasive approaches [21]. Compared with percutaneous catheter drainage followed by video-assisted retroperitoneal debridement, endoscopic catheter drainage followed by endoscopic necrosectomy resulted in lower rates of cardiovascular organ failure and pancreatic fistula, and a shorter hospital stay, but similar mortality and major morbidity rates. About half of the patients in each group responded to catheter drainage alone without debridement. We believe that the optimal approach to management of infected pancreatic necrosis should be determined by disease and patient characteristics, and that these patients should be treated at a tertiary center where all options are likely to be available. (See "Pancreatic debridement", section on 'Minimally invasive approach to pancreatic debridement'.)

Partial pancreaticoduodenectomy versus duodenum-preserving pancreatic head resection for chronic pancreatitis (September 2017)

Head-dominant chronic pancreatitis can be treated surgically with either partial pancreaticoduodenectomy or duodenum-preserving pancreatic head resection (DPPHR). In a multicenter randomized trial (ChroPac), the two procedures resulted in similar quality of life at 24 months with no significant differences in major morbidity and mortality rates [22]. DPPHR resulted in shorter operative time (4.7 versus 5.3 hours), but more readmissions due to chronic pancreatitis (27 versus 11 percent). Given that both procedures are equally effective and morbid, surgeons should choose based on their experience and the patient's anatomical and clinical conditions. (See "Surgery for chronic pancreatitis", section on 'Head-dominant disease'.)

Early refeeding in acute pancreatitis (August 2017)

The optimal timing of refeeding in acute pancreatitis is uncertain. In a systematic review of 11 randomized trials that included 948 patients with acute pancreatitis, early refeeding (≤48 hours after hospitalization) did not increase adverse effects or exacerbate symptoms compared with delayed refeeding [23]. In four of seven trials that included patients with mild to moderate pancreatitis, it reduced length of hospital stay. However, there was significant heterogeneity in feeding protocols and reported outcomes, and several studies had a high risk of bias. Additional randomized trials are needed to define the benefits of early enteral nutrition in acute pancreatitis. (See "Management of acute pancreatitis", section on 'Oral'.)

SMALL BOWEL AND COLONIC DISEASE

Lifestyle factors and the risk of diverticulitis (December 2017)

The cumulative impact of multiple risk factors on the incidence of diverticulitis has not been previously evaluated. In an observational study that included over 50,000 men, each additional low-risk lifestyle factor (low red meat intake, high dietary fiber, normal body mass index [BMI], vigorous physical activity, and no smoking history) incrementally reduced the risk of diverticulitis [24]. Overall, adherence to a low-risk lifestyle was associated with a 50 percent lower risk of diverticulitis. (See "Colonic diverticulosis and diverticular disease: Epidemiology, risk factors, and pathogenesis", section on 'Risk factors'.)

AGA guidelines on therapeutic drug monitoring in inflammatory bowel disease (October 2017)

The American Gastroenterological Association (AGA) has published guidelines on therapeutic drug monitoring in inflammatory bowel disease (IBD) [25]. It suggests thiopurine methyltransferase (TPMT) testing (enzymatic activity or genotype) prior to initiating thiopurines in adults to guide dosing. For adults with active IBD despite treatment with tumor necrosis factor-alpha inhibitors, the AGA also suggests monitoring drug trough levels and, in some cases, anti-drug antibodies to guide treatment changes. (See "Infliximab in Crohn disease" and "6-mercaptopurine (6-MP) metabolite monitoring and TPMT testing in patients with inflammatory bowel disease", section on 'Introduction'.)

Eculizumab in early-onset protein-losing enteropathy associated with inherited CD55 deficiency (July 2017)

Protein-losing enteropathy is characterized by an excessive loss of serum proteins into the gastrointestinal tract and can be caused by a diverse group of disorders. Whole genome sequencing of 11 patients with early-onset protein-losing enteropathy and primary intestinal lymphangiectasia has identified novel homozygous loss of function mutations in the gene encoding CD55 (decay activating factor). This autosomal recessively inherited syndrome is characterized by CD55 deficiency, hyperactivation of complement, angiopathic thrombosis, and early-onset protein-losing enteropathy (CHAPLE syndrome) [26]. In a separate case report, three patients in a family with CHAPLE syndrome were treated with eculizumab, a humanized monoclonal antibody to C5 [27]. Within 100 days of initiation of therapy there was reduction in complement activation, increase in serum albumin and total protein concentration, and improvement in diarrhea. While these data suggest the importance of complement activation in a subset of patients with protein-losing enteropathy, the role of complement blockade in the treatment of protein-losing gastroenteropathy is unclear. (See "Protein-losing gastroenteropathy", section on 'Treatment of the underlying disease'.)

OTHER GASTROENTEROLOGY AND NUTRITION

IDSA guidelines on acute diarrhea (November 2017)

The Infectious Diseases Society of America updated its guidelines on the diagnosis and management of infectious diarrhea [28]. They recommend confirmatory stool culture and susceptibility testing when culture-independent diagnostic tests are positive for clinically important bacterial pathogens. They highlight the need for careful interpretation of multiplex molecular panels, which simultaneously test for multiple organisms by detecting genetic material, do not always indicate infection with a viable organism, and frequently identify more than one potential pathogen. The guidelines also emphasize reserving empiric antibiotic therapy for select patients, including those with severe illness or immunocompromising conditions. Our approach is generally consistent with these guidelines. (See "Approach to the adult with acute diarrhea in resource-rich settings".)

Frequency for dosing of oral iron (November 2017)

For many years, iron deficiency has been treated with oral iron given at least once per day, despite significant gastrointestinal side effects in the majority of individuals. A small, unblinded randomized trial has now demonstrated that giving oral iron every other day rather than every day resulted in greater iron absorption and fewer gastrointestinal side effects [29]. Alternate-day dosing is also supported by mechanistic studies that showed favorable effects on hepcidin, a negative regulator of intestinal iron absorption and iron release from macrophages. We now suggest that patients treated with oral iron for iron deficiency take the iron every other day rather than daily. (See "Treatment of iron deficiency anemia in adults", section on 'Dosing and administration (oral iron)'.)

Self-administered hypnotherapy for functional abdominal pain in children and adolescents (June 2017)

Increasing evidence suggests that gut-directed hypnotherapy reduces pain frequency and intensity in children and adolescents with functional abdominal pain disorders (FAPDs). In a trial of this therapy that randomly assigned children (age 8 to 18 years) with FAPDs to a self-administered home-based approach using a compact disc or to individual therapy with a qualified therapist for three months, over 60 percent of each group had ≥50 percent reduction in pain frequency and intensity at one-year follow-up [30]. These findings suggest that self-directed hypnotherapy is a reasonable option for children and adolescents with FAPDs, particularly if trained therapists are not available. (See "Functional abdominal pain in children and adolescents: Management in primary care", section on 'Improved coping'.)

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REFERENCES

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