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What's new in gastroenterology and hepatology
Official reprint from UpToDate® ©2015 UpToDate®
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What's new in gastroenterology and hepatology

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.

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All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Oct 2015. | This topic last updated: Nov 04, 2015.

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.


Laparoscopic versus open surgery for rectal cancer (October 2015)

Curative resection of a rectal carcinoma was traditionally carried out with open techniques. Although earlier randomized trials had shown that laparoscopic rectal cancer surgery was equivalent to open surgery, two subsequent trials failed to prove that laparoscopic surgery is non-inferior to open surgery [1,2]. In the two more recent trials, successful resections, defined as simultaneously achieving negative distal and circumferential margins as well as a complete total mesorectal excision, were achieved in approximately 82 percent with laparoscopic surgery versus 87 to 89 percent with open surgery. Given the conflicting results, the best surgical approach to treating rectal cancer needs to be determined individually by tumor and patient characteristics, as well as surgeon experience. When performing laparoscopic rectal surgery for cancer, surgeons should have a low threshold for converting to open surgery when difficulties arise with dissection. (See "Surgical resection of primary rectal adenocarcinoma", section on 'Laparoscopic versus open approach'.)


Oral recombinant H. pylori vaccine (October 2015)

In a randomized phase 3 trial, 4464 H. pylori uninfected children (ages 6 to 15 years) were assigned to a three-dose oral recombinant H. pylori vaccine or placebo [3]. At one year, the incidence of H. pylori infection was significantly lower in the vaccine group. Among patients who completed extended follow-up, H. pylori acquisition continued to be lower in vaccinated as compared with unvaccinated children, but protection levels were lower in the second and third year. There were no serious adverse events related to the vaccine. Additional studies with long-term follow-up are needed to validate these results. (See "Pathophysiology of and immune response to Helicobacter pylori infection", section on 'Vaccination'.)

Prediction model for eosinophilic esophagitis (September 2015)

The distinction between eosinophilic esophagitis and gastroesophageal reflux disease is often difficult to make. A prediction model that incorporated eight clinical and endoscopic features (younger age; male sex; presence of dysphagia and food allergies; presence of esophageal rings, furrows, and plaques; and lack of a hiatal hernia) predicted eosinophilic esophagitis with an accuracy, sensitivity, and specificity of 84, 97, and 92 percent, respectively [4]. However, additional studies are needed to validate this model. (See "Clinical manifestations and diagnosis of eosinophilic esophagitis", section on 'Distinction from GERD'.)


Hepatic decompensation associated with ombitasvir-paritaprevir-ritonavir for chronic HCV infection (November 2015)

With more widespread use of ombitasvir-paritaprevir-ritonavir with or without dasabuvir for patients with chronic hepatitis C virus (HCV) genotypes 1 and 4 infection, reports of associated hepatic injury and decompensation have emerged [5]. Most cases occurred in patients with existing cirrhosis and within one to four weeks of drug initiation; some cases resulted in death or need for liver transplantation. Patients with compensated cirrhosis who use this regimen should be monitored closely for signs of decompensation and undergo interval transaminase and bilirubin testing after initiation. The regimen is contraindicated in individuals with Child B and C class cirrhosis. (See "Direct-acting antivirals for the treatment of hepatitis C virus infection", section on 'Ombitasvir-paritaprevir-ritonavir with or without dasabuvir'.)

Primary biliary cirrhosis is now known as primary biliary cholangitis (October 2015)

The term "primary biliary cirrhosis" has been used to describe the T-lymphocyte-mediated attack on small intralobular bile ducts. However, the terminology is changing to "primary biliary cholangitis" to describe the disorder and its natural history more accurately [6]. With the advent of treatment with ursodeoxycholic acid, the majority of patients now have normal life expectancies and only a minority of patients develops cirrhosis. (See "Clinical manifestations, diagnosis, and prognosis of primary biliary cholangitis (primary biliary cirrhosis)", section on 'Introduction'.)

Daclatasvir-based regimens for genotype 3 HCV infection (August 2015)

In the era of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, patients with genotype 3 infection have emerged as a difficult-to-treat population, with suboptimal sustained virologic response (SVR) rates with short courses of previously available regimens. In July 2015, the US Food and Drug Administration approved the use of the novel NS5A inhibitor daclatasvir in combination with sofosbuvir for genotype 3 HCV infection. This agent has been available in Europe and elsewhere. Daclatasvir plus sofosbuvir for 12 weeks is now our preferred regimen for genotype 3-infected patients without cirrhosis. In an open-label study that included 120 such patients, SVR rates were 96 percent with that regimen [7]. SVR rates were only 63 percent in the 32 patients with cirrhosis included in the study, although limited evidence suggests that efficacy is enhanced with the addition of ribavirin to the regimen [8,9]. Thus, daclatasvir plus sofosbuvir plus weight-based ribavirin is our preferred regimen for genotype 3-infected patients with cirrhosis; the regimen is given for 24 weeks, although the optimal duration is uncertain. Sofosbuvir plus peginterferon plus ribavirin for 12 weeks is an effective alternative for patients willing to take interferon and has more established efficacy data. Sofosbuvir plus ribavirin for 24 weeks can also result in acceptably high SVR rates for treatment-naïve patients with cirrhosis. (See "Treatment regimens for chronic hepatitis C virus genotypes 2 and 3", section on 'Genotype 3'.)

Terlipressin versus midodrine and octreotide for hepatorenal syndrome (July 2015)

Terlipressin, a vasopressin analog, is used for the treatment of hepatorenal syndrome, but is not approved for use in the United States. In a trial that randomly assigned 49 patients with hepatorenal syndrome to terlipressin plus albumin or to midodrine and octreotide plus albumin, the rate of complete response (a decrease in serum creatinine to less than 1.5 mg/dL [133 micromol/L] at 14 days) was significantly greater with terlipressin plus albumin (56 versus 5 percent) [10]. However, the partial response rate was greater with midodrine and octreotide plus albumin, and mortality rates did not differ; in addition, the dose of midodrine used was lower than often employed in clinical practice, and blood pressures were lower in the group who received midodrine and octreotide plus albumin. Thus, despite this and other limited trials showing benefit from terlipressin, it remains unclear whether this therapy is superior to the combination of midodrine and octreotide. (See "Hepatorenal syndrome", section on 'Terlipressin plus albumin where available'.)

Direct-acting antiviral therapy for HCV in HIV-infected patients (July 2015)

Although HIV-infected patients had lower response rates to chronic hepatitis C virus (HCV) treatment with peginterferon and ribavirin compared with HIV-uninfected patients, a growing number of studies have demonstrated that HIV/HCV coinfection is not associated with worse response to direct-acting antiviral-based regimens. Most recently, the regimen of ledpasvir-sofosbuvir for 12 weeks and the regimen of the investigational NS5A inhibitor daclatasvir with sofosbuvir for 12 weeks were each reported to result in sustained virologic response (SVR) rates exceeding 90 percent among HIV/HCV coinfected patients, including those who had failed prior HCV treatment and those with cirrhosis [11,12]. The efficacy and safety in these studies are comparable to those observed among HCV monoinfected patients. Potential drug interactions with antiretroviral agents remain a major consideration when selecting HCV treatment regimens in HIV-infected patients. (See "Treatment of hepatitis C virus infection in the HIV-infected patient", section on 'Genotype 1 infection'.)


Pentoxifylline in severe acute pancreatitis (August 2015)

Severe acute pancreatitis has a high mortality rate. In a randomized trial, 28 patients with predicted severe acute pancreatitis were assigned to pentoxifylline or placebo within 72 hours of diagnosis [13]. Patients treated with pentoxifylline had fewer intensive care unit admissions and hospital stays longer than four days as compared with placebo. However, there were no significant differences in the levels of inflammatory markers between the two groups. Studies are needed to validate these results and define the role of pentoxifylline in the treatment of acute pancreatitis. (See "Management of acute pancreatitis", section on 'Other'.)

International consensus on management of IgG4-related disease (July 2015)

The optimal treatment for immunoglobulin G4-related disease (IgG4-RD) has not been established, nor have randomized trials been performed to inform treatment approaches. Nonetheless, broad international consensus has been achieved among experts on several major management strategies [14]. These include the importance of biopsy confirmation of the diagnosis to exclude malignancy and other disorders that may mimic IgG4-RD; the need to treat symptomatic patients, sometimes urgently, as well as some asymptomatic patients; use of glucocorticoids as first-line therapy; use of maintenance therapy in certain patients; and retreatment strategies for patients who relapse after successful remission induction. Consensus was not reached on the use of steroid-sparing immunosuppressive agents from the start of treatment, and largely reflects different practice styles between countries. (See "Overview of IgG4-related disease", section on 'Diagnostic studies' and "Overview of IgG4-related disease", section on 'Treatment principles and observations'.)


Curcumin for induction of remission in ulcerative colitis (July 2015)

Curcumin is an investigational agent that may have a protective role in ulcerative colitis through modulation of the release of tumor necrosis factor-alpha and nitric oxide. In a randomized trial, 50 patients with active mild to moderate ulcerative colitis who did not respond to two weeks of maximum-dose oral and topical mesalamine therapy were assigned to additional treatment with curcumin or placebo for one month [15]. At four weeks, patients in the curcumin group had significantly higher rates of clinical and endoscopic remission as compared with the placebo group. However, curcumin can alter the stool color in some patients, and the exceptionally low response rates in the placebo group (ie, none responded) raise concern that blinding was not adequate. Additional studies are needed to support the use of curcumin in patients with ulcerative colitis. (See "Approach to adults with steroid-refractory and steroid-dependent ulcerative colitis", section on 'Curcumin'.)

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 [16]. 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'.)


Mechanical bowel preparation and oral antibiotics prior to elective colon surgery (September 2015)

Traditionally, mechanical bowel preparation was used with oral antibiotics to prepare for all elective colon surgeries. After several randomized trials reported no benefit from mechanical bowel preparation (MBP) without antibiotics, colon resection without preoperative bowel preparation and without oral antibiotics became widespread. A retrospective study of data from over 8000 patients undergoing colorectal resection found that MBP combined with oral antibiotics, compared with MBP alone, was associated with lower rates of anastomotic leak, and that MBP, with or without antibiotics, was associated with lower rates of surgical site infection and postoperative ileus compared with no preparation prior to surgery [17]. One drawback is a potential increase in the rate of Clostridium difficile infection for patients treated with oral antibiotics.

Thus, for patients undergoing elective colon surgeries, we suggest mechanical bowel preparation combined with oral antibiotics. Mechanical bowel preparation is usually accomplished with polyethylene glycol solution and is followed by oral antibiotics such as neomycin and erythromycin base. Administering oral antibiotics in the absence of mechanical bowel preparation is of unproven benefit and is not advised. (See "Overview of colon resection", section on 'Bowel preparation'.)

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  1. Fleshman J, Branda M, Sargent DJ, et al. Effect of Laparoscopic-Assisted Resection vs Open Resection of Stage II or III Rectal Cancer on Pathologic Outcomes: The ACOSOG Z6051 Randomized Clinical Trial. JAMA 2015; 314:1346.
  2. Stevenson AR, Solomon MJ, Lumley JW, et al. Effect of Laparoscopic-Assisted Resection vs Open Resection on Pathological Outcomes in Rectal Cancer: The ALaCaRT Randomized Clinical Trial. JAMA 2015; 314:1356.
  3. Zeng M, Mao XH, Li JX, et al. Efficacy, safety, and immunogenicity of an oral recombinant Helicobacter pylori vaccine in children in China: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2015; 386:1457.
  4. Dellon ES, Rusin S, Gebhart JH, et al. A Clinical Prediction Tool Identifies Cases of Eosinophilic Esophagitis Without Endoscopic Biopsy: A Prospective Study. Am J Gastroenterol 2015; 110:1347.
  5. FDA Drug Safety Communication: FDA warns of serious liver injury risk with hepatitis C treatments Viekira Pak and Technivie. October 22, 2015. (Accessed on October 22, 2015).
  6. Beuers U, Gershwin ME, Gish RG, et al. Changing nomenclature for PBC: From 'cirrhosis' to 'cholangitis'. Hepatology 2015; 62:1620.
  7. Nelson DR, Cooper JN, Lalezari JP, et al. All-oral 12-week treatment with daclatasvir plus sofosbuvir in patients with hepatitis C virus genotype 3 infection: ALLY-3 phase III study. Hepatology 2015; 61:1127.
  8. Foster GR, McLaughlan J, Irving W, et al.Treatment of decompensated HCV cirrhosis in patients with diverse genotypes: 12 weeks of sofosbuvir and NS5A inhibitors with/without ribavirin is effective in HCV genotypes 1 and 3.Presented at the 50th Annual Meeting of the European Association for the Study of the Liver (EASL), Vienna Austria, April 22-26, 2015. Abstract O002
  9. Poordad F, Schiff ER, Vierling JM, et al. Daclatasvir, sofosbuvir, and ribavirin combination for HCV patients with advanced cirrhosis or post-transplant recurrence: ALLY-1 phase 3 study. Presented at the 50th Annual Meeting of the European Association for the Study of the Liver (EASL), Vienna Austria, April 22-26, 2015.
  10. Cavallin M, Kamath PS, Merli M, et al. Terlipressin plus albumin versus midodrine and octreotide plus albumin in the treatment of hepatorenal syndrome: A randomized trial. Hepatology 2015; 62:567.
  11. Naggie S, Cooper C, Saag M, et al. Ledipasvir and Sofosbuvir for HCV in Patients Coinfected with HIV-1. N Engl J Med 2015; 373:705.
  12. Wyles DL, Ruane PJ, Sulkowski MS, et al. Daclatasvir plus Sofosbuvir for HCV in Patients Coinfected with HIV-1. N Engl J Med 2015; 373:714.
  13. Vege SS, Atwal T, Bi Y, et al. Pentoxifylline Treatment in Severe Acute Pancreatitis: A Pilot, Double-Blind, Placebo-Controlled, Randomized Trial. Gastroenterology 2015; 149:318.
  14. Khosroshahi A, Wallace ZS, Crowe JL, et al. International Consensus Guidance Statement on the Management and Treatment of IgG4-Related Disease. Arthritis Rheumatol 2015; 67:1688.
  15. Lang A, Salomon N, Wu JC, et al. Curcumin in Combination With Mesalamine Induces Remission in Patients With Mild-to-Moderate Ulcerative Colitis in a Randomized Controlled Trial. Clin Gastroenterol Hepatol 2015; 13:1444.
  16. 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.
  17. Kiran RP, Murray AC, Chiuzan C, et al. Combined preoperative mechanical bowel preparation with oral antibiotics significantly reduces surgical site infection, anastomotic leak, and ileus after colorectal surgery. Ann Surg 2015; 262:416.
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