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'.)
SMALL BOWEL AND COLONIC DISEASE
Larazotide for persistent symptoms of celiac disease (June 2015)
A significant proportion of patients with celiac disease have persistent symptoms due to inadvertent gluten exposure. Larazotide acetate is an investigational oral peptide that modulates intestinal tight junctions. In a randomized trial, 342 adults with celiac disease on a gluten-free diet were assigned to three different doses of larazotide or placebo for 12 weeks to relieve ongoing symptoms . The lowest dose was effective in reducing Celiac Disease Gastrointestinal Symptom Rating Scale scores (the primary endpoint), as well as reducing the number of symptomatic days, severity of abdominal pain, and related nongastrointestinal symptoms, and was well tolerated. Additional studies are needed to confirm these findings and determine optimal dosing. (See "Management of celiac disease in adults", section on 'Poor compliance or inadvertent gluten ingestion'.)
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'.)
- Nan H, Hutter CM, Lin Y, et al. Association of aspirin and NSAID use with risk of colorectal cancer according to genetic variants. JAMA 2015; 313:1133.
- Syngal S, Brand RE, Church JM, et al. ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol 2015; 110:223.
- Centers for Disease Control and Prevention (CDC). Notes from the Field: New Delhi metallo-β-lactamase-producing Escherichia coli associated with endoscopic retrograde cholangiopancreatography - Illinois, 2013. MMWR Morb Mortal Wkly Rep 2014; 62:1051.
- Epstein L, Hunter JC, Arwady MA, et al. New Delhi metallo-β-lactamase-producing carbapenem-resistant Escherichia coli associated with exposure to duodenoscopes. JAMA 2014; 312:1447.
- http://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/ucm434871.htm (Accessed on February 27, 2015).
- Rutala WA, Weber DJ. Gastrointestinal endoscopes: a need to shift from disinfection to sterilization? JAMA 2014; 312:1405.
- http://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/ucm434871.htm (Accessed on March 04, 2015).
- http://www.cdc.gov/hai/organisms/cre/cre-duodenoscope-surveillance-protocol.html?zbrandid=439&zidType=CH&zid=9357704&zsubscriberId=93262298&zbdom=http://www.informz.net (Accessed on March 13, 2015).
- Rex DK, Schoenfeld PS, Cohen J, et al. Quality indicators for colonoscopy. Gastrointest Endosc 2015; 81:31.
- Kim HG, Thosani N, Banerjee S, et al. Effect of prior biopsy sampling, tattoo placement, and snare sampling on endoscopic resection of large nonpedunculated colorectal lesions. Gastrointest Endosc 2015; 81:204.
- US Food and Drug Administration (FDA) news release. FDA approves breath test to aid in diagnosis of delayed gastric emptying. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm441370.htm (Accessed on April 07, 2015).
- Szarka LA, Camilleri M, Vella A, et al. A stable isotope breath test with a standard meal for abnormal gastric emptying of solids in the clinic and in research. Clin Gastroenterol Hepatol 2008; 6:635.
- Thursz MR, Richardson P, Allison M, et al. Prednisolone or pentoxifylline for alcoholic hepatitis. N Engl J Med 2015; 372:1619.
- Zeuzem S, Ghalib R, Reddy KR, et al. Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic HCV Genotype 1, 4, or 6 Infection: A Randomized Trial. Ann Intern Med 2015.
- Sulkowski M, Hezode C, Gerstoft J, et al. Efficacy and safety of 8 weeks versus 12 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin in patients with hepatitis C virus genotype 1 mono-infection and HIV/hepatitis C virus co-infection (C-WORTHY): a randomised, open-label phase 2 trial. Lancet 2015; 385:1087.
- Lawitz E, Gane E, Pearlman B, et al. Efficacy and safety of 12 weeks versus 18 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin for hepatitis C virus genotype 1 infection in previously untreated patients with cirrhosis and patients with previous null response with or without cirrhosis (C-WORTHY): a randomised, open-label phase 2 trial. Lancet 2015; 385:1075.
- JK Rockstroh, M Nelson, C Katlama, et al. C-EDGE co-infected: phase 3 study of grazoprevir/elbasvir in patients with HCV/HIV. Presented at the 2015 International Liver Congress: 50th Annual Meeting of the European Association for the Study of the Liver (EASL). Vienna, April 22-26, 2015. Abstract P0887.
- Jacobson, F Poordad, R Firpi-Morell, et al. Efficacy and safety af grazoprevir and elbasvir in hepatitis C genotype 1-infected patients with Child-Pugh class B cirrhosis (C-SALT Part A). Presented at the 2015 International Liver Congress: 50th Annual Meeting of the European Association for the Study of the Liver (EASL). Vienna, April 22-26, 2015. Abstract O008.
- D Roth, D Nelson, A Bruchfeld, et al. C-SURFER: grazoprevir plus elbasvir in treatment-naive and treatment-experienced patients with hepatitis C virus genotype 1 infection and chronic kidney disease. Presented at the 2015 International Liver Congress: 50th Annual Meeting of the European Association for the Study of the Liver (EASL). Vienna, April 22-26, 2015. Abstract LP02.
- Poordad F, Sievert W, Mollison L, et al. Fixed-dose combination therapy with daclatasvir, asunaprevir, and beclabuvir for noncirrhotic patients with HCV genotype 1 infection. JAMA 2015; 313:1728.
- Muir AJ, Poordad F, Lalezari J, et al. Daclatasvir in combination with asunaprevir and beclabuvir for hepatitis C virus genotype 1 infection with compensated cirrhosis. JAMA 2015; 313:1736.
- Angeli P, Ginès P, Wong F, et al. Diagnosis and management of acute kidney injury in patients with cirrhosis: revised consensus recommendations of the International Club of Ascites. J Hepatol 2015; 62:968.
- Karvellas CJ, Abraldes JG, Arabi YM, et al. Appropriate and timely antimicrobial therapy in cirrhotic patients with spontaneous bacterial peritonitis-associated septic shock: a retrospective cohort study. Aliment Pharmacol Ther 2015; 41:747.
- Johnson PJ, Berhane S, Kagebayashi C, et al. Assessment of liver function in patients with hepatocellular carcinoma: a new evidence-based approach-the ALBI grade. J Clin Oncol 2015; 33:550.
- Wong F, Leung W, Al Beshir M, et al. Outcomes of patients with cirrhosis and hepatorenal syndrome type 1 treated with liver transplantation. Liver Transpl 2015; 21:300.
- Hartl J, Ehlken H, Weiler-Normann C, et al. Patient selection based on treatment duration and liver biochemistry increases success rates after treatment withdrawal in autoimmune hepatitis. J Hepatol 2015; 62:642.
- Osinusi A, Townsend K, Kohli A, et al. Virologic response following combined ledipasvir and sofosbuvir administration in patients with HCV genotype 1 and HIV co-infection. JAMA 2015; 313:1232.
- Sulkowski MS, Eron JJ, Wyles D, et al. Ombitasvir, paritaprevir co-dosed with ritonavir, dasabuvir, and ribavirin for hepatitis C in patients co-infected with HIV-1: a randomized trial. JAMA 2015; 313:1223.
- Leffler DA, Kelly CP, Green PH, et al. Larazotide acetate for persistent symptoms of celiac disease despite a gluten-free diet: a randomized controlled trial. Gastroenterology 2015; 148:1311.
- Monteleone G, Neurath MF, Ardizzone S, et al. Mongersen, an oral SMAD7 antisense oligonucleotide, and Crohn's disease. N Engl J Med 2015; 372:1104.
- Gibson DJ, Heetun ZS, Redmond CE, et al. An accelerated infliximab induction regimen reduces the need for early colectomy in patients with acute severe ulcerative colitis. Clin Gastroenterol Hepatol 2015; 13:330.