Disclosures: Peter A L Bonis, MD Nothing to disclose. Anne C Travis, MD, MSc, FACG, AGAF Equity Ownership/Stock Options: Proctor & Gamble [Peptic ulcer disease, esophageal reflux (omeprazole)]. Shilpa Grover, MD, MPH Nothing to disclose.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.
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.
Aspirin/NSAID use and risk of colorectal cancer by genotype (March 2015)
It has been unclear if the effect of aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) on colorectal cancer (CRC) risk varies by genotype. In a case control study that included 8634 cases and 8553 controls pooled from 10 observational studies, regular use of aspirin, NSAIDs, or both was associated with a decreased risk of CRC . Among individuals with the single-nucleotide polymorphism (SNP) rs2965667-TT genotype, regular use of aspirin/NSAIDs was also associated with a decreased risk of CRC. However, among individuals with a TA or AA genotype, which constituted 4 percent of the study population, the use of aspirin/NSAIDs was associated with an increased risk of CRC. As compared with nonregular aspirin/NSAID use, regular use in individuals with rs16973225-AA genotype, but not the AC or CC genotypes, was associated with a decreased risk of CRC. Additional studies are needed to validate this gene-environment interaction and define population subgroups that can benefit from the chemopreventive effect of aspirin/NSAIDs. (See "NSAIDs (including aspirin): Role in prevention of colorectal cancer", section on 'Biologic basis'.)
American College of Gastroenterology guidelines for hereditary gastrointestinal cancer (February 2015)
In February 2015, the American College of Gastroenterology issued recommendations for genetic testing and management of hereditary gastrointestinal cancer syndromes . These guidelines highlight the need for genetic evaluation for an adenomatous polyposis syndrome in individuals with >10 cumulative colorectal adenomas and evaluation of mismatch repair deficiency in all newly diagnosed colorectal cancers. (See "Familial adenomatous polyposis: Screening and management of patients and families", section on 'Genetic testing' and "Lynch syndrome (hereditary nonpolyposis colorectal cancer): Clinical manifestations and diagnosis", section on 'Diagnostic evaluation'.)
Infection associated with contaminated endoscopes (October 2014, MODIFIED February 2015)
In January 2014, the Centers for Disease Control and Prevention (CDC) reported that 69 cases of New Delhi metallo-beta-lactamase (NDM)-producing carbapenem-resistant Enterobacteriaceae (CRE) had been identified in the United States (44 from northeastern Illinois) in the previous year . Further investigation identified 39 cases from one hospital . Sporadic cases have been subsequently reported to the US Food and Drug Administration (FDA) . The source of infection has been 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 [4,6]. 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 and facilities should adhere to reprocessing and surveillance guidelines issued by the Centers for Disease Control and Prevention, the US Food and Drug Administration, and professional societies, such as the American Gastroenterological Association. If a patient is diagnosed with a multidrug-resistant organism following ERCP, the duodenoscope that was used for the procedure should be removed from service until it is verified to be free of pathogens [7,8]. (See "Endoscope disinfection", section on 'Carbapenem-resistant Enterobacteriaceae'.)
Increase in target adenoma detection rates for colonoscopy (January 2015)
Adenoma detection rates (ADRs) are important quality measures for endoscopists performing colonoscopies. Previously, it was recommended that endoscopists have ADRs of at least 25 percent for men and 15 percent for women. However, some studies suggested higher rates may be appropriate. In an updated guideline, the American Society for Gastrointestinal Endoscopy and the American College of Gastroenterology have increased their ADR target to at least 25 percent overall (30 percent in men and 20 percent in women) . (See "Overview of colonoscopy in adults", section on 'Quality indicators'.)
Prior manipulation of large colon polyps associated with failed endoscopic mucosal resection (December 2014)
The removal of large colon polyps during endoscopy raises a number of concerns, including the risk of inadequate polypectomy. This is important because large polyps have an increased risk of harboring invasive carcinoma. A new study suggests that manipulation of large colon lesions prior to referring patients for endoscopic mucosal resection lowers complete resection rates and increases recurrence rates . Specifically, prior manipulations such as tattooing the lesion site and incomplete snare resection of the lesion are associated with low complete resection rates and high recurrence rates (50 and 54 percent, respectively). This study suggests that manipulation of large colon polyps should be avoided during the initial colonoscopy if endoscopic mucosal resection is likely to be needed for complete polyp removal. In particular, attempts should not be made to partially remove the lesion or to place a tattoo directly at the site of the lesion. (See "Endoscopic removal of large colon polyps", section on 'Effect of prior polyp manipulation'.)
ESOPHAGEAL AND GASTRIC DISEASE
Breath test for gastroparesis (April 2015)
The spirulina 13C breath test was approved by the United States Food and Drug Administration to diagnose gastroparesis in April 2015 . Approval was based on a study of 115 patients who underwent simultaneous scintigraphy and spirulina 13C breath test. At 80 percent specificity, the 13C-spirulina breath test samples (at 150 and 180 minutes) had a combined sensitivity of 89 percent for delayed gastric emptying . However, additional studies are needed to validate these results before 13C breath tests can be used routinely. (See "Gastroparesis: Etiology, clinical manifestations, and diagnosis", section on 'Alternatives to scintigraphy'.)
Efficacy of pentoxifylline for severe alcoholic hepatitis remains unclear (May 2015)
In untreated patients with severe alcoholic hepatitis (Maddrey discriminant function ≥32), short-term mortality rates are high (up to 45 percent at one month). Current management options include prednisolone and pentoxifylline. However, the efficacy of pentoxifylline is unclear. The STOPAH trial is the largest trial to date to compare treatments for severe alcoholic hepatitis . It included 1103 patients who were treated with prednisolone, pentoxifylline, both drugs, or neither drug. A trend toward a survival benefit was seen in patients who received prednisolone, but not in those who received pentoxifylline. However, the trial excluded sicker patients, including those with renal failure that did not stabilize within the first seven days, and the mortality rate in the placebo arm (17 percent) was lower than seen in other trials. This raises the possibility that the patients included in the trial were not representative of patients with severe alcoholic hepatitis in general. As a result, the efficacy of pentoxifylline in patients with severe alcoholic hepatitis remains unclear. Our approach is to use prednisolone for most patients with severe alcoholic hepatitis, but to use pentoxifylline in patients who have contraindications to the use of glucocorticoids. (See "Alcoholic hepatitis: Natural history and management", section on 'Pentoxifylline'.)
Investigational fixed-dose combination therapies for chronic HCV infection (May 2015)
Drug development for chronic hepatitis C virus (HCV) infection continues at a rapid pace and is yielding new, simple, and highly effective regimens that are both interferon- and ribavirin-free. Recent studies of such regimens have demonstrated the following:
●A once-daily, single-pill combination of the NS3/4A protease inhibitor grazoprevir and the NS5A inhibitor elbasvir given for 12 weeks resulted in sustained virological response (SVR) rates greater than 90 percent among treatment-naïve and experienced genotype 1-infected patients with and without cirrhosis [14-16]. The addition of ribavirin to the regimen did not appear to substantially improve outcomes. Data on this regimen in patients with HIV coinfection, Child-Pugh Class B cirrhosis, severe renal impairment, and genotype 4 or 6 infection are also very promising [17-19]. This regimen is not expected to be available until 2016. (See "Investigational therapies for hepatitis C virus infection", section on 'Grazoprevir and elbasvir'.)
●A single-pill combination of the NS5A inhibitor daclatasvir, the NS3/4A protease inhibitor asunaprevir, and the non-nucleoside NS5B inhibitor beclasvir given twice daily for 12 weeks resulted in SVR rates of 92 and 89 percent among treatment-naïve and experienced genotype 1-infected patients without cirrhosis . A trial among patients with cirrhosis suggested that response rates are even higher when this regimen is combined with ribavirin . (See "Investigational therapies for hepatitis C virus infection", section on 'Daclatasvir and asunaprevir combinations'.)
Diagnostic criteria for hepatorenal syndrome (April 2015)
The International Club of Ascites has altered their diagnostic criteria for hepatorenal syndrome . The new criteria recognize that, in such patients, acute kidney injury can sometimes be characterized by small absolute increases in serum creatinine. (See "Hepatorenal syndrome", section on 'Diagnosis'.)
Increased mortality with delayed treatment for spontaneous bacterial peritonitis (April 2015)
Patients with spontaneous bacterial peritonitis (SBP) who develop septic shock have high mortality rates, but early initiation of antimicrobial therapy may result in improved outcomes. In a retrospective study of patients with cirrhosis and SBP-associated septic shock, the risk of mortality nearly doubled (1.9-fold increase) with every hour delay in administering antimicrobial therapy . In patients with suspected SBP-associated sepsis, ascitic fluid cultures should be obtained immediately and empiric antimicrobial therapy initiated to maximize the patient's chance of survival. (See "Spontaneous bacterial peritonitis in adults: Treatment and prophylaxis", section on 'Prognosis'.)
New ALBI model to assess liver function in patients with HCC (March 2015)
Hepatocellular carcinoma (HCC) is a complex disease that most often arises on a background of chronic liver disease. The complex interplay between the tumor and liver function influences prognosis, and liver function is an important consideration in treatment selection. The most commonly used model to assess severity of liver function (the Child-Turcotte-Pugh [CP] score), has never been validated in patients with HCC. A new model based upon serum albumin and bilirubin alone (the ALBI score) provides a simple, objective, and more discriminatory method of assessing liver function in patients with HCC than does the CP score; it was validated in geographically distinct cohorts of patients undergoing a range of treatments, including surgery for localized HCC and sorafenib for advanced disease . The objective nature and simplicity of ALBI may diminish interobserver variation (as occurs with grading of ascites and encephalopathy in the CP scoring system) and help to refine prognostic estimates in patients treated for HCC, particularly among those with better liver function. (See "Staging and prognostic factors in hepatocellular carcinoma", section on 'ALBI score'.)
Resolution of hepatorenal syndrome after liver transplantation (March 2015)
Resolution of type 1 hepatorenal syndrome was examined in 62 patients undergoing liver transplantation at a single center over a 10 year period . Of these, resolution of hepatorenal syndrome occurred in 47 patients (76 percent). The remaining patients either died or required long-term dialysis. The mean duration of dialysis prior to liver transplantation was the only significant predictor of resolution (10 days among those who resolved versus 25 days among those who did not). (See "Hepatorenal syndrome", section on 'Improving hepatic function'.)
Aminotransferase levels predict relapse in autoimmune hepatitis (February 2015)
Patients with autoimmune hepatitis who achieve remission with immunosuppressive therapy have a 50 to 90 percent chance of relapsing within 12 months if immunosuppression is withdrawn. Alanine aminotransferase (ALT) levels prior to drug withdrawal may predict which patients are more likely to achieve long-term remission. This was examined in a series of 28 patients who had been in remission with normal ALT levels for at least 24 months prior to drug withdrawal . Of the 15 patients who achieved long-term remission, all had ALT levels that were <2 times the upper limit of normal at the time of drug withdrawal, whereas among the 13 who relapsed, only three had ALT levels <2 times the upper limit of normal. This study may help further guide decisions about drug withdrawal in patients with autoimmune hepatitis who are in remission. (See "Autoimmune hepatitis: Treatment", section on 'Patients in remission'.)
Interferon-free regimens to treat HCV in HIV/HCV coinfected patients (February 2015)
Patients coinfected with HIV and hepatitis C virus (HCV) traditionally had lower response rates to HCV treatment with peginterferon and ribavirin compared with individuals without HIV infection. However, with the use of direct-acting antiviral (DAA) agents in HCV treatment, HIV infection is no longer a negative predictor of response. In two studies of HIV/HCV genotype 1 coinfected individuals, sustained virological response rates to two interferon-free DAA regimens (ledipasvir-sofosbuvir or ombitasvir-paritaprevir-ritonavir and dasabuvir plus ribavirin) were greater than 90 percent, comparable to rates in populations infected with HCV alone [27,28]. The major consideration in HCV antiviral regimen selection for HIV/HCV coinfected patients is the potential for drug interactions between antiretroviral and HCV antiviral agents. (See "Treatment of hepatitis C virus infection in the HIV-infected patient", section on 'Genotype 1 infection'.)
Preventing hepatitis B virus reactivation in patients receiving chemotherapy (February 2015)
When patients with serologic evidence of hepatitis B virus (HBV) infection need immunosuppressive therapy for other reasons, antiviral therapy may be warranted to decrease the risk of HBV reactivation. We favor prophylaxis with entecavir or tenofovir over lamivudine in such cases because these agents have more potent antiviral activity and are less likely to select for drug resistant virus. This preference is supported by results of a trial in which 121 HBV surface antigen (HBsAg) positive patients were randomly assigned to prophylactic antiviral therapy with entecavir or lamivudine prior to receiving chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone for diffuse large B-cell lymphoma . The rates of HBV-related hepatitis and HBV reactivation were lower among those who received entecavir. (See "Hepatitis B virus reactivation associated with immunosuppressive therapy", section on 'Which agents to use'.)
Interferon-free regimens for chronic genotype 1 HCV infection (December 2013, MODIFIED January 2015)
Several highly effective and well tolerated interferon-free options are now available for chronic genotype 1 hepatitis C virus (HCV) infection. Ledipasvir-sofosbuvir, ombitasvir-paritaprevir-ritonavir plus dasabuvir, and simeprevir plus sofosbuvir all achieve sustained virologic response (SVR) rates, and thus effective cure, in excess of 90 percent in genotype 1 infected patients [30-38]. The duration of the regimen and the decision of whether to add weight-based ribavirin depend on the treatment history, presence of cirrhosis, and, for the ombitasvir-paritaprevir-ritonavir plus dasabuvir regimen, the infecting subtype (1a or 1b) (algorithm 1). The choice between the regimens depends primarily on the potential for drug interactions and drug toxicity. Additionally, in the United States, options will be limited by the individual's insurance provider. If cost or insurance coverage is not an issue, we generally favor the regimen of ledipasvir-sofosbuvir for its favorable adverse effect profile, its minimal drug interactions, and its ease of administration (a single pill once daily). (See "Treatment regimens for chronic hepatitis C virus genotype 1", section on 'Selection of treatment regimens'.)
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 . (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 individual data of 15 studies of patients with PBC, increased alkaline phosphatase and bilirubin levels were associated with decreased transplant-free survival . This meta-analysis supports using these surrogate endpoints in PBC treatment trials. (See "Clinical manifestations, diagnosis, and prognosis of primary biliary cirrhosis", section on 'Prognostic factors'.)
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 . 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'.)
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 . 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'.)
SMALL BOWEL AND COLONIC DISEASE
Mongersen for the treatment of active Crohn disease (March 2015)
Antisense oligonucleotides are nucleic acid sequences that bind to RNA or DNA with a high degree of specificity and can thereby block expression of a specific protein. A randomized phase 2 trial evaluated the efficacy of mongersen, an investigational oral SMAD7 antisense oligonucleotide, for the treatment of active Crohn disease. In this randomized trial, 166 patients were assigned to receive three different doses of mongersen or placebo daily for two weeks . The primary outcomes were clinical remission at day 15, defined as a Crohn Disease Activity Index (CDAI) score <150, with maintenance of remission for at least two weeks, and the safety of mongersen treatment. Clinical remission rates were significantly greater in patients treated with higher doses of mongersen as compared with placebo. Clinical response rates were greater among patients receiving mongersen at any dose as compared with placebo. Most adverse events were related to complications and symptoms of Crohn disease. However, inclusion in the study was based on CDAI scores at baseline and not endoscopic confirmation of active Crohn disease. Additional studies are needed to confirm these findings and define the role of mongersen in the treatment of Crohn disease. (See "Investigational therapies in the medical management of Crohn disease", section on 'Antisense oligonucleotides'.)
Accelerated infliximab induction in patients with acute severe ulcerative colitis (February 2015)
The optimal infliximab regimen for induction of remission in acute severe ulcerative colitis (UC) is not known. A retrospective study of 50 hospitalized patients with steroid-refractory acute severe UC compared colectomy rates with standard infliximab dosing compared with an accelerated dosing regimen consisting of three induction doses of infliximab within a median period of 24 days . Although colectomy rates during induction therapy were significantly lower with the accelerated regimen, there were no significant differences in colectomy rates between the groups during the following two years. Thus, additional studies are needed to identify the optimal anti-TNF dosing for the induction and maintenance of remission in patients with severe UC with the goal of decreasing the need for colectomy. (See "Approach to adults with steroid-refractory and steroid-dependent ulcerative colitis", section on 'Steroid-refractory ulcerative colitis'.)
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 . 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'.)
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