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What's new in gastroenterology and hepatology

What's new in gastroenterology and hepatology
Authors:
Anne C Travis, MD, MSc, FACG, AGAF
Shilpa Grover, MD, MPH, AGAF
Kristen M Robson, MD, MBA, FACG
Literature review current through: Feb 2022. | This topic last updated: Feb 18, 2022.

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.

ESOPHAGEAL AND GASTRIC DISEASE

Proton pump inhibitors for Barrett's esophagus (February 2022)

Data on proton pump inhibitors (PPIs) for preventing progression of Barrett's esophagus have been mixed. In a meta-analysis of 12 studies including over 155,000 patients with Barrett's esophagus, PPI use was associated with a significantly lower risk of progression to high-grade dysplasia and/or esophageal adenocarcinoma compared with no PPI (adjusted odds ratio 0.47) [1]. These data support our approach of using indefinite PPI therapy for all patients with Barrett's esophagus, including those with asymptomatic acid reflux. (See "Barrett's esophagus: Surveillance and management", section on 'Management of acid reflux'.)

Secretin stimulation testing in suspected Zollinger-Ellison syndrome (November 2021)

In patients being evaluated for Zollinger-Ellison syndrome (ZES), discontinuation of proton pump inhibitors (PPIs) is recommended before a secretin stimulation test (SST). In a retrospective study of SSTs that compared test performance on versus off PPIs, the sensitivity, specificity, and positive predictive value were comparable with no false positive or negative results on PPI therapy [2]. However, the majority of patients had a high pretest probability of ZES due to MEN1 syndrome. We continue to suggest PPI cessation for 1 week prior to SST for ZES but administer high-dose H2 receptor antagonists until 12 to 30 hours prior to the test and only perform testing once active ulcers have healed, as stopping a PPI in patients with ZES can cause massive acid hypersecretion and lead to acute ulcer complications. (See "Zollinger-Ellison syndrome (gastrinoma): Clinical manifestations and diagnosis", section on 'Secretin stimulation test'.)

Updated ACG guidelines on gastroesophageal reflux disease (November 2021)

Updated American College of Gastroenterology guidelines on gastroesophageal reflux disease (GERD) recommend an empiric eight-week trial of proton pump inhibitors (PPI) in patients with classic GERD symptoms without alarm features and suggest a diagnostic endoscopy for those who do not respond adequately [3]. They also recommend attempts at discontinuation of PPIs after eight weeks in asymptomatic patients without Barrett's esophagus or erosive esophagitis. Our recommendations are largely consistent with these guidelines. (See "Medical management of gastroesophageal reflux disease in adults", section on 'PPI refractory symptoms'.)

HEPATOLOGY

Optimizing the Model for End-stage Liver Disease (MELD) score (February 2022)

The Model for End-stage Liver Disease (MELD) score is used to predict short-term mortality and thereby inform allocation of livers for transplantation. An updated score, termed MELD 3.0, includes new variables such as female sex and serum albumin and lowers the serum creatinine cutoff [4]. In a large registry study of patients awaiting liver transplantation, MELD 3.0 had relatively high predictive accuracy and slightly outperformed MELD-Sodium (MELD-Na) in predicting 90-day waiting list mortality. MELD 3.0 reassigned 9 percent of decedents to a higher score category, possibly giving them a greater chance of transplantation. This study suggests that MELD 3.0 shows promise for improving organ allocation and lowering waiting list mortality. (See "Model for End-stage Liver Disease (MELD)", section on 'MELD 3.0'.)

Bariatric surgery versus nonsurgical management of NASH in patients with obesity (January 2022)

Nonalcoholic steatohepatitis (NASH) is a common cause of chronic liver disease, and obesity is a major risk factor for developing NASH. In the SPLENDOR study of over 1000 patients with histologically confirmed NASH and obesity, gastric bypass or sleeve gastrectomy was associated with a significantly lower 10-year cumulative incidence of major adverse liver outcomes (2.3 versus 9.6 percent) and major cardiovascular events (8.5 versus 15.7 percent) compared with nonsurgical management [5]. The general approach to NASH in patients with obesity is lifestyle modification and weight loss; if that fails, bariatric surgery is the best alternative. (See "Outcomes of bariatric surgery", section on 'Nonalcoholic fatty liver disease'.)

Ursodeoxycholic acid for primary biliary cholangitis with cirrhosis (October 2021)

Ursodeoxycholic acid (UDCA) is first-line therapy for patients with primary biliary cholangitis (PBC). However, the benefits of UDCA for PBC complicated by cirrhosis have been uncertain. In a study including 501 patients with PBC and compensated cirrhosis, an adequate biochemical response to UDCA (defined as alkaline phosphatase <1.67 times the upper limit of normal after 24 months of therapy) was associated with lower risk of hepatic decompensation, all-cause mortality, and liver-related mortality or transplantation compared with a minimal or no response [6]. These data support the value of UDCA for patients with PBC and cirrhosis who show an adequate biochemical response to therapy. (See "Overview of the management of primary biliary cholangitis", section on 'Initial therapy'.)

Updated guidance on spontaneous bacterial peritonitis (October 2021)

Patients with cirrhosis complicated by ascites are at increased risk for spontaneous bacterial peritonitis (SBP). The American Association for the Study of Liver Diseases (AASLD) updated practice guidance on SBP emphasizes performing diagnostic abdominal paracentesis when SBP is suspected, promptly initiating empiric antibiotic therapy, infusing albumin when the diagnosis is established, and tailoring antimicrobial therapy based on fluid culture results (algorithm 1) [7]. Our approach to the diagnosis and management of SBP is generally consistent with this guidance. (See "Spontaneous bacterial peritonitis in adults: Treatment and prophylaxis", section on 'Introduction'.)

Plasma not helpful for mildly elevated INR (October 2021)

A new trial has documented the lack of benefit from using plasma to "correct" an increased prothrombin time (PT) and international normalized ratio (INR). The trial randomly assigned 57 hospitalized adults with an INR of 1.5 to 2.5 (approximately 60 percent with cirrhosis) who were undergoing a procedure outside the operating room to receive or not receive plasma [8]. There was little to no difference in post-procedure hemoglobin (a measure of bleeding), hospital length of stay, or adverse events. Although small, this trial adds further evidence that plasma should not be used to treat a mildly elevated INR. Appropriate uses of plasma include massive transfusion protocols, therapeutic plasma exchange, and treatment of bleeding due to one or more deficient clotting factors when a specific factor concentrate is unavailable. (See "Clinical use of plasma components", section on 'Settings in which plasma is not appropriate'.)

Biliary tract injury after severe COVID-19 (August 2021)

Liver involvement in COVID-19 is often associated with elevated aminotransferases; biliary tract injury has been identified as a late complication. In a study of over 2000 hospitalized patients with COVID-19, 12 of those with severe infection developed cholangiopathy characterized by cholestasis and biliary tract abnormalities at a mean 118 days after COVID-19 diagnosis [9]. Imaging findings included inflammation, stricturing, and dilation of the biliary tree. Five patients with persistent jaundice, hepatic insufficiency, and/or recurrent cholangitis were evaluated for liver transplantation, and one patient underwent a transplant. Further studies are needed to understand the pathogenesis and to identify preventive and therapeutic measures for COVID-19-related cholangiopathy. (See "COVID-19: Issues related to liver disease in adults", section on 'Liver-related chronic complications'.)

PANCREATIC AND BILIARY DISEASE

Catheter drainage in patients with infected pancreatic necrosis (November 2021)

Whether patients with infected pancreatic necrosis have better outcomes with early catheter drainage is unclear. In a randomized trial of 104 such patients comparing immediate with delayed drainage (until necrotic collections were largely encapsulated but patients were clinically deteriorating or not improving), both approaches had similar complication and mortality rates; however, immediate drainage resulted in a higher number of interventions [10]. Approximately one-third of patients improved with antibiotics without the need for intervention. These data support our approach to selectively perform nonsurgical drainage in patients with infected pancreatic necrosis who exhibit clinical deterioration or fail to improve with antibiotics, and delay drainage in clinically stable patients until the development of walled-off necrosis. (See "Management of acute pancreatitis", section on 'Acute necrotic collection and walled-off necrosis'.)

SMALL BOWEL AND COLONIC DISEASE

Novel microbiome therapeutic for recurrent Clostridioides difficile infection (February 2022)

Oral microbiome therapeutics are being investigated as a safer and less invasive approach than fecal microbiota transplant for preventing Clostridioides difficile infection (CDI) recurrence. In a randomized trial including 182 patients with multiple recurrent CDI who had resolution of symptoms after treatment with standard-of-care antibiotics, an oral capsule composed of live purified Firmicutes spores (SER-109) decreased recurrence rates (12 versus 40 percent with placebo) up to eight weeks after treatment [11]. Although the outcome of CDI recurrence is notable, we await further data and regulatory approval prior to routine use of this agent. (See "Fecal microbiota transplantation for treatment of Clostridioides difficile infection", section on 'Specific bacterial FMT'.)

Inflammatory bowel disease and response to COVID-19 vaccination (January 2022)

Data on the immunogenicity of COVID-19 vaccines in patients with inflammatory bowel disease (IBD) are emerging. In a study of nearly 600 adults with IBD who received mRNA SARS-CoV-2 vaccination, 99 percent who were tested two weeks after the second vaccine dose had detectable antibodies, regardless of medication regimen (ie, biologic therapy, small molecule therapy, immunomodulator therapy, and/or glucocorticoids) [12]. For patients with IBD, this study demonstrates high rates of initial humoral response, provides reassurance for those on immunosuppressive medications, and supports our recommendation for vaccination. (See "COVID-19: Issues related to gastrointestinal disease in adults", section on 'COVID-19 vaccination'.)

Updated guidelines on management of fecal incontinence (November 2021)

Updated American College of Gastroenterology guidelines on the management of fecal incontinence (FI) emphasize recognizing the underlying causes, using antidiarrheal medications for FI associated with diarrhea, using fiber and/or laxatives for FI associated with constipation, and biofeedback for patients who do not respond to initial measures [13]. Interventions such as injectable bulking agents, sacral nerve stimulation, and mechanical barrier devices are reserved for patients who do not respond to biofeedback. Our approach is generally consistent with these guidelines. (See 'Fecal incontinence in adults: Management'.)

Ozanimod for moderate to severe ulcerative colitis (October 2021)

Ozanimod, an oral small molecule, is under investigation for treating ulcerative colitis (UC). In an induction trial including over 600 patients with moderate to severe UC, clinical remission rates at 10 weeks were higher with ozanimod compared with placebo (18 versus 6 percent) [14]. Overall rates of adverse events were numerically similar in both induction groups, although statistical analysis was not provided. In a maintenance trial including over 400 patients, ozanimod resulted in higher rates of clinical remission at 52 weeks (37 versus 18 percent). Increased alanine aminotransferase levels (in the absence of drug-induced liver injury) were reported more frequently with ozanimod maintenance therapy. These data are promising; further studies will help inform the role of ozanimod for UC management. (See "Management of moderate to severe ulcerative colitis in adults", section on 'Ozanimod'.)

New guidelines for the diagnosis of pouchitis (October 2021)

Pouchitis is common in patients with ulcerative colitis who have undergone restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA). The International Ileal Pouch Consortium has published new guidelines to address the diagnosis and classification of pouch disorders [15]. The diagnosis of pouchitis is suspected in patients with increased stool frequency and urgency and is established by endoscopic findings that demonstrate active inflammation of the pouch (ulceration, mucosal erythema, friability). Disease characteristics (eg, duration of symptoms, frequency of flares, response to antibiotics) are used to classify pouchitis and help guide treatment. Our approach to patients with suspected pouchitis is consistent with these guidelines. (See "Pouchitis: Epidemiology, pathogenesis, clinical features, and diagnosis", section on 'Introduction'.)

Clinical practice update for surveillance of colorectal dysplasia in inflammatory bowel disease (October 2021)

Patients with inflammatory bowel disease (IBD) are at increased risk for colorectal cancer (CRC). The American Gastroenterological Association (AGA) has published updated practice advice for surveillance in patients with IBD to incorporate evidence from the past decade [16]. It addresses timing for initial surveillance colonoscopy (ie, 8 to 10 years after IBD diagnosis or immediately for patients with coexisting primary sclerosing cholangitis) and optimizing detection of dysplasia by controlling mucosal inflammation, adequate bowel preparation, and biopsy protocols that include targeted sampling of mucosal irregularities. Our approach to surveillance colonoscopy for patients with IBD is generally consistent with AGA practice statements. (See "Surveillance and management of dysplasia in patients with inflammatory bowel disease", section on 'Introduction'.)

Effectiveness of SARS-CoV-2 vaccine in patients with inflammatory bowel disease (September 2021)

Most patients with inflammatory bowel disease (IBD) on immune-modifying therapy are eligible for the COVID-19 vaccine; however, the immune response in this patient population is uncertain. In a study of nearly 15,000 patients with IBD, full vaccination status (ie, >7 days after second dose of mRNA vaccine) but not partial vaccination was associated with lower rates of SARS-CoV-2 infection compared with no vaccination (0.11 versus 1.34 percent) [17]. Vaccine effectiveness did not differ by IBD medication exposure, which included patients on mesalamine, biologic agents, thiopurines, methotrexate, or glucocorticoids. These findings underscore the importance of full SARS-CoV-2 vaccination for reducing risk of COVID-19 in patients with IBD. (See "COVID-19: Issues related to gastrointestinal disease in adults", section on 'COVID-19 vaccination'.)

Filgotinib for moderate to severe ulcerative colitis (August 2021)

Filgotinib, an oral small molecule, is under investigation for treating ulcerative colitis (UC). In two induction trials including a total of over 1300 patients with moderate to severe UC, filgotinib 200 mg daily resulted in higher rates of clinical remission compared with placebo after 10 weeks (biologic therapy-naïve patients: 26 versus 15 percent; biologic therapy-experienced patients: 12 versus 4 percent) [18]. In the maintenance trial, filgotinib 200 mg daily resulted in higher rates of sustained clinical remission after 58 weeks (37 versus 11 percent). While these data are promising, further studies and regulatory approval are needed before incorporating filgotinib into routine clinical practice. (See "Management of moderate to severe ulcerative colitis in adults", section on 'Investigational therapies'.)

OTHER GASTROENTEROLOGY AND NUTRITION

PPI use and inflammatory bowel disease (November 2021)

Due to their ability to alter the gut microbiome, proton pump inhibitors (PPI) may impact the risk of inflammatory bowel disease (IBD). In a study that included >600,000 individuals followed for a median of 12 years, regular PPI use was associated with an increased risk of IBD compared with nonusers; however, the absolute risk of IBD was low [19]. We continue to recommend prescribing PPIs at the lowest effective dose and for the shortest duration appropriate to the condition being treated. (See "Proton pump inhibitors: Overview of use and adverse effects in the treatment of acid related disorders", section on 'Inflammatory bowel disease'.)

REFERENCES

  1. Chen Y, Sun C, Wu Y, et al. Do proton pump inhibitors prevent Barrett's esophagus progression to high-grade dysplasia and esophageal adenocarcinoma? An updated meta-analysis. J Cancer Res Clin Oncol 2021; 147:2681.
  2. Bhattacharya S, Blau JE, Cochran C, et al. Validity of Secretin Stimulation Testing on Proton Pump Inhibitor Therapy for Diagnosis of Zollinger-Ellison Syndrome. Am J Gastroenterol 2021; 116:2216.
  3. Katz PO, Dunbar KB, Schnoll-Sussman FH, et al. ACG Clinical Guideline for the Diagnosis and Management of Gastroesophageal Reflux Disease. Am J Gastroenterol 2022; 117:27.
  4. Kim WR, Mannalithara A, Heimbach JK, et al. MELD 3.0: The Model for End-Stage Liver Disease Updated for the Modern Era. Gastroenterology 2021; 161:1887.
  5. Aminian A, Al-Kurd A, Wilson R, et al. Association of Bariatric Surgery With Major Adverse Liver and Cardiovascular Outcomes in Patients With Biopsy-Proven Nonalcoholic Steatohepatitis. JAMA 2021; 326:2031.
  6. John BV, Khakoo NS, Schwartz KB, et al. Ursodeoxycholic Acid Response Is Associated With Reduced Mortality in Primary Biliary Cholangitis With Compensated Cirrhosis. Am J Gastroenterol 2021; 116:1913.
  7. Biggins SW, Angeli P, Garcia-Tsao G, et al. Diagnosis, Evaluation, and Management of Ascites, Spontaneous Bacterial Peritonitis and Hepatorenal Syndrome: 2021 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology 2021; 74:1014.
  8. Carson JL, Ness PM, Pagano MB, et al. Plasma trial: Pilot randomized clinical trial to determine safety and efficacy of plasma transfusions. Transfusion 2021; 61:2025.
  9. Faruqui S, Okoli FC, Olsen SK, et al. Cholangiopathy After Severe COVID-19: Clinical Features and Prognostic Implications. Am J Gastroenterol 2021; 116:1414.
  10. Boxhoorn L, van Dijk SM, van Grinsven J, et al. Immediate versus Postponed Intervention for Infected Necrotizing Pancreatitis. N Engl J Med 2021; 385:1372.
  11. Feuerstadt P, Louie TJ, Lashner B, et al. SER-109, an Oral Microbiome Therapy for Recurrent Clostridioides difficile Infection. N Engl J Med 2022; 386:220.
  12. Melmed GY, Botwin GJ, Sobhani K, et al. Antibody Responses After SARS-CoV-2 mRNA Vaccination in Adults With Inflammatory Bowel Disease. Ann Intern Med 2021; 174:1768.
  13. Wald A, Bharucha AE, Limketkai B, et al. ACG Clinical Guidelines: Management of Benign Anorectal Disorders. Am J Gastroenterol 2021; 116:1987.
  14. Sandborn WJ, Feagan BG, D'Haens G, et al. Ozanimod as Induction and Maintenance Therapy for Ulcerative Colitis. N Engl J Med 2021; 385:1280.
  15. Shen B, Kochhar GS, Kariv R, et al. Diagnosis and classification of ileal pouch disorders: consensus guidelines from the International Ileal Pouch Consortium. Lancet Gastroenterol Hepatol 2021; 6:826.
  16. Murthy SK, Feuerstein JD, Nguyen GC, Velayos FS. AGA Clinical Practice Update on Endoscopic Surveillance and Management of Colorectal Dysplasia in Inflammatory Bowel Diseases: Expert Review. Gastroenterology 2021; 161:1043.
  17. Khan N, Mahmud N. Effectiveness of SARS-CoV-2 Vaccination in a Veterans Affairs Cohort of Patients With Inflammatory Bowel Disease With Diverse Exposure to Immunosuppressive Medications. Gastroenterology 2021; 161:827.
  18. Feagan BG, Danese S, Loftus EV Jr, et al. Filgotinib as induction and maintenance therapy for ulcerative colitis (SELECTION): a phase 2b/3 double-blind, randomised, placebo-controlled trial. Lancet 2021; 397:2372.
  19. Xia B, Yang M, Nguyen LH, et al. Regular Use of Proton Pump Inhibitor and the Risk of Inflammatory Bowel Disease: Pooled Analysis of 3 Prospective Cohorts. Gastroenterology 2021; 161:1842.
Topic 8351 Version 10977.0

References

1 : Do proton pump inhibitors prevent Barrett's esophagus progression to high-grade dysplasia and esophageal adenocarcinoma? An updated meta-analysis.

2 : Validity of Secretin Stimulation Testing on Proton Pump Inhibitor Therapy for Diagnosis of Zollinger-Ellison Syndrome.

3 : ACG Clinical Guideline for the Diagnosis and Management of Gastroesophageal Reflux Disease.

4 : MELD 3.0: The Model for End-Stage Liver Disease Updated for the Modern Era.

5 : Association of Bariatric Surgery With Major Adverse Liver and Cardiovascular Outcomes in Patients With Biopsy-Proven Nonalcoholic Steatohepatitis.

6 : Ursodeoxycholic Acid Response Is Associated With Reduced Mortality in Primary Biliary Cholangitis With Compensated Cirrhosis.

7 : Diagnosis, Evaluation, and Management of Ascites, Spontaneous Bacterial Peritonitis and Hepatorenal Syndrome: 2021 Practice Guidance by the American Association for the Study of Liver Diseases.

8 : Plasma trial: Pilot randomized clinical trial to determine safety and efficacy of plasma transfusions.

9 : Cholangiopathy After Severe COVID-19: Clinical Features and Prognostic Implications.

10 : Immediate versus Postponed Intervention for Infected Necrotizing Pancreatitis.

11 : SER-109, an Oral Microbiome Therapy for Recurrent Clostridioides difficile Infection.

12 : Antibody Responses After SARS-CoV-2 mRNA Vaccination in Adults With Inflammatory Bowel Disease.

13 : ACG Clinical Guidelines: Management of Benign Anorectal Disorders.

14 : Ozanimod as Induction and Maintenance Therapy for Ulcerative Colitis.

15 : Diagnosis and classification of ileal pouch disorders: consensus guidelines from the International Ileal Pouch Consortium.

16 : AGA Clinical Practice Update on Endoscopic Surveillance and Management of Colorectal Dysplasia in Inflammatory Bowel Diseases: Expert Review.

17 : Effectiveness of SARS-CoV-2 Vaccination in a Veterans Affairs Cohort of Patients With Inflammatory Bowel Disease With Diverse Exposure to Immunosuppressive Medications.

18 : Filgotinib as induction and maintenance therapy for ulcerative colitis (SELECTION): a phase 2b/3 double-blind, randomised, placebo-controlled trial.

19 : Regular Use of Proton Pump Inhibitor and the Risk of Inflammatory Bowel Disease: Pooled Analysis of 3 Prospective Cohorts.