What's new in gastroenterology and hepatology

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.

ENDOSCOPY

Motorized spiral enteroscopy for evaluating small bowel disorders (October 2023)

Device-assisted enteroscopy facilitates direct access to the small bowel, but studies on motorized spiral enteroscopy are limited. In a trial comparing motorized spiral enteroscopy with single balloon enteroscopy in 110 adults with suspected small bowel disorders, rates of complete small bowel examination were higher with motorized spiral enteroscopy (71 versus 11 percent) [1]. Motorized spiral enteroscopy also resulted in higher diagnostic yield (80 versus 62 percent) and shorter mean procedure times (58 versus 114 minutes). No major adverse events occurred in either group. These data show promise, but further studies on safety are needed before performing motorized spiral enteroscopy routinely in clinical practice. In addition, its use may be limited by equipment availability and endoscopic expertise. (See "Overview of deep small bowel enteroscopy", section on 'Motorized spiral enteroscopy'.)

ESOPHAGEAL AND GASTRIC DISEASE

Rifabutin triple therapy for Helicobacter pylori (October 2023)

Management of patients who have failed multiple antibiotic regimens for Helicobacter pylori is an increasingly frequent challenge. In a randomized trial in which 364 subjects with H. pylori who failed at least two prior treatments were assigned to rifabutin triple therapy or bismuth quadruple therapy for 14 days, H. pylori eradication rates were similar in both groups [2]. However, the rifabutin group had a higher compliance rate and a lower rate of adverse effects. This trial supports current guidelines and our recommendation to use rifabutin triple therapy as a salvage treatment for H. pylori. (See "Treatment regimens for Helicobacter pylori in adults", section on 'Salvage regimens'.)

HEPATOLOGY

Mortality risk in alcohol-associated liver disease (January 2024)

Few studies have reported the long-term outcomes of patients with alcohol-associated liver disease (ALD). In a national registry study including over 23,000 patients with ALD diagnosed at median age 58 years, 67 percent died during >100,000 person-years of follow-up and liver disease was the primary cause of death in 45 percent [3]. The 5- and 10-year mortality rates due to liver disease were 26 and 31 percent, respectively. These data emphasize the importance of treating patients with alcohol use disorder and may inform strategies to prevent liver-related mortality in those with ALD. (See "Management of alcohol-associated steatosis and alcohol-associated cirrhosis", section on 'Mortality'.)

Model for End-stage Liver Disease (MELD) 3.0 for liver transplantation (October 2023, Modified December 2023)

The Model for End-stage Liver Disease (MELD) score is used to allocate livers for transplantation. Recently, the Organ Procurement and Transplantation Network implemented an updated score, MELD 3.0, for prioritizing liver transplantation candidates who are ages 12 and older [4]. MELD 3.0 includes variables from the original model (ie, serum bilirubin, serum creatinine, and international normalized ratio) in addition to other inputs (ie, serum sodium, patient sex, and serum albumin) and a lower creatinine ceiling. Goals of using MELD 3.0 include reducing overall waitlist mortality and improving access for female liver transplant candidates. (See "Model for End-stage Liver Disease (MELD)", section on 'MELD 3.0'. and "Liver transplantation for hepatocellular carcinoma", section on 'MELD 3.0'.)

Paracentesis for hospitalized patients with cirrhosis and ascites (November 2023)

Patients with cirrhosis complicated by ascites are at risk for spontaneous bacterial peritonitis and other complications. However, the magnitude of risk associated with deferring diagnostic paracentesis in such patients when they are hospitalized is uncertain. In a large database study comparing late (ie, ≥24 hours) or no paracentesis with early paracentesis in hospitalized patients with ascites, late paracentesis or no paracentesis was associated with higher risk of acute kidney injury (odds ratio [OR] 2.2 and 1.3, respectively) and inpatient mortality (OR 1.5 and 1.4, respectively) [5]. These data support performing diagnostic paracentesis within 24 hours of hospital admission, which is consistent with our practice. (See "Diagnostic and therapeutic abdominal paracentesis", section on 'Indications'.)

Sugar-sweetened beverages and risk of liver cancer (September 2023)

There is interest in evaluating the impact of sugar-sweetened beverages (such as regular sodas and fruit drinks) on the risk of developing liver cancer. In an observational study of almost 99,000 postmenopausal females, higher intake of sugar-sweetened beverages (one or more servings per day) was associated with an increased risk of developing liver cancer (hazard ratio 1.85) relative to less frequent consumption (three or less servings per month) [6]. These findings support the importance of limiting or avoiding sugar-sweetened beverages as part of a healthy diet for adults and for cancer prevention. (See "Epidemiology and risk factors for hepatocellular carcinoma", section on 'Dietary factors'.)

Gene therapy for Crigler-Najjar syndrome (September 2023)

Gene therapy for Crigler-Najjar syndrome is directed at restoring sufficient UGT1A1 activity to maintain serum bilirubin in a safe range. In an open-label study of five young adults with Crigler-Najjar syndrome and severe hyperbilirubinemia managed with daily phototherapy (two with adjunctive phenobarbital), gene therapy was administered at one of two doses [7]. For the three participants in the high-dose cohort, the mean total bilirubin concentrations declined from 20.5 mg/dL (351 micromol/L) with phototherapy to 8.7 mg/dL (149 micromol/L) without phototherapy by 80 weeks. There were transient increases in liver enzymes, managed with immunosuppressive therapy, and no serious adverse events. Further studies are needed to determine the indications, optimal protocol, and long-term efficacy and safety of gene therapy. (See "Crigler-Najjar syndrome", section on 'Investigational therapies'.)

PANCREATIC AND BILIARY DISEASE

Risk of pancreatic cancer in stable intraductal papillary mucinous neoplasms (November 2023)

The optimal duration of pancreatic cancer surveillance in patients with branch duct intraductal papillary mucinous neoplasms (BD-IPMNs) is unclear. In a study of over 3800 such patients without worrisome features (WFs) or high-risk stigmata (HRS), 42 percent had BD-IPMNs that remained stable in size and did not develop WF/HRS for at least five years [8]. Within this group, patients ≥75 years with cysts <30 mm and those ≥65 years with cysts <15 mm had a standardized incidence ratio for pancreatic cancer comparable to the general population and low disease-specific mortality. These data suggest that this subgroup may be able to discontinue pancreatic cancer surveillance; however, further studies are needed to validate these results. (See "Intraductal papillary mucinous neoplasm of the pancreas (IPMN): Pathophysiology and clinical manifestations", section on 'Pancreatic malignancy'.)

Microscopic colitis and acute pancreatitis (November 2023)

Microscopic colitis has been associated with several other conditions. In a recent population-based study including >12,000 patients with microscopic colitis, these individuals had a twofold increased risk for acute pancreatitis unrelated to gallstones but no increase in gallstone-related acute pancreatitis compared with matched controls [9]. The increased risk persisted for more than 10 years after diagnosis. Whether the increase in acute pancreatitis was due to active disease or a side effect of budesonide is unclear. Further studies are needed to evaluate this association. (See "Microscopic (lymphocytic and collagenous) colitis: Clinical manifestations, diagnosis, and management", section on 'Associated conditions'.)

Clinical practice update on exocrine pancreatic insufficiency (November 2023)

The American Gastroenterological Association (AGA) recently published best practice advice on exocrine pancreatic insufficiency (EPI) [10]. The AGA Clinical Practice Update advises considering a diagnosis of EPI in individuals with moderate-risk clinical conditions (eg, celiac disease, previous intestinal surgery, longstanding diabetes mellitus, Zollinger-Ellison syndrome). It emphasizes the importance of testing for EPI in patients with nonspecific symptoms and cautions against relying on a response to an empiric trial of pancreatic enzymes to diagnose EPI as this may be due to a placebo effect. Our approach is consistent with this guidance. (See "Exocrine pancreatic insufficiency", section on 'Diagnostic approach'.)

SMALL BOWEL AND COLONIC DISEASE

Mirikizumab for moderate to severe ulcerative colitis (August 2023, Modified January 2024)

Therapeutic options for adults with moderate to severe ulcerative colitis (UC) are expanding. In an induction trial comparing mirikizumab (a monoclonal antibody that targets the p19 subunit of interleukin-23) with placebo in nearly 1300 patients, mirikizumab (300 mg intravenously every four weeks) resulted in higher rates of clinical remission after 12 weeks (24 versus 13 percent) [11]. In the maintenance trial including over 500 patients, mirikizumab (200 mg subcutaneously every four weeks) resulted in higher rates of clinical remission after 40 weeks (50 versus 25 percent). Based on these data, the US Food and Drug Administration approved mirikizumab for moderate to severe UC [12]. We anticipate using mirikizumab as first- or second-line therapy for adults with moderate to severe UC. (See "Management of moderate to severe ulcerative colitis in adults", section on 'Anti-interleukin antibody-based therapy'.)

Clinical practice update on risk stratification for colorectal cancer screening and postpolypectomy surveillance (December 2023)

The American Gastroenterological Association (AGA) recently published nine statements of best practice advice on risk stratification for colorectal cancer (CRC) screening and postpolypectomy surveillance [13]. They advise basing risk stratification on an individual's age, a known or suspected predisposing hereditary CRC syndrome, other CRC predisposing conditions (eg, inflammatory bowel disease), and/or a family history of CRC. They also suggest that the decision to continue postpolypectomy surveillance for individuals older than 75 years should be individualized. Shared decision-making discussions should include an assessment of the risks of incident CRC, procedure-related risks, comorbidities, and life expectancy (>5 years). Our approach is consistent with this guidance. (See "Overview of colon polyps", section on 'Risk assessment for subsequent colorectal cancer'.)

Investigational therapy for irritable bowel syndrome with bile acid diarrhea (November 2023)

Patients with irritable bowel syndrome with predominant diarrhea (IBS-D) frequently have concurrent bile acid malabsorption. In a randomized trial in which 31 patients with IBS and bile acid diarrhea were assigned to aldafermin (an investigational analogue of recombinant human fibroblast growth factor 19) or placebo for 28 days, the aldafermin group had lower bile acid synthesis and improved stool consistency during week 4 of treatment, but abdominal pain and stool frequency were not significantly different for the two groups [14]. Treatment-related adverse events were significantly higher in patients in the aldafermin group, and four patients on aldafermin had a clinically significant increase in low-density lipoprotein cholesterol. More studies are needed to clarify if aldafermin has a role in the treatment of IBS-D. (See "Treatment of irritable bowel syndrome in adults", section on 'Other therapies'.)

Low-dose tricyclic antidepressants in irritable bowel syndrome (October 2023)

The efficacy of tricyclic antidepressants (TCAs) in the management of irritable bowel syndrome (IBS) has not been well established in the primary care setting. In a pragmatic randomized trial, 463 patients with IBS unresponsive to dietary advice and first-line therapies in primary care practices were assigned to titrated low-dose amitriptyline or placebo as a second-line therapy [15]. At six months, patients treated with low-dose amitriptyline had lower IBS-symptom severity scores and a higher rate of symptom relief. The most common side effects were related to the anticholinergic effects of amitriptyline, but the majority were mild. These data support current guidelines and our recommendation to use TCAs in the management of patients with IBS. (See "Treatment of irritable bowel syndrome in adults", section on 'Antidepressants'.)

Pozelimab for CD55-deficient protein losing enteropathy (October 2023)

Protein-losing enteropathies (PLE) are characterized by excessive loss of serum proteins into the gastrointestinal tract, resulting in hypoproteinemia, edema, and pleural and pericardial effusions. Pozelimab, a C5 inhibitor, has been approved by the US Food and Drug Administration (FDA) to treat patients with CD55-deficient PLE (CHAPLE syndrome) based on an ongoing single-arm phase II/III clinical trial of 10 patients with CHAPLE syndrome and symptomatic hypoalbuminemia [16]. All patients achieved normalization of albumin by week 12 of treatment with pozelimab and maintained serum albumin concentrations within the normal range through at least 72 weeks. Improvements were also reported in serum IgG levels and total iron-binding capacity. Although FDA approved, long-term safety data are still needed. (See "Protein-losing gastroenteropathy", section on 'Treatment of the underlying disease'.)

Guidelines on chronic idiopathic constipation (July 2023)

The American College of Gastroenterology and American Gastroenterological Association updated guidelines on the management of chronic idiopathic constipation (CIC) include use of fiber as first-line therapy and the use of stimulant laxatives for short-term use and rescue therapy [17]. Options for CIC refractory to over-the-counter agents include lubiprostone, linaclotide, plecanatide, and prucalopride. Our recommendations are largely consistent with these guidelines. (See "Management of chronic constipation in adults", section on 'Bulk-forming laxatives'.)

OTHER GASTROENTEROLOGY AND NUTRITION

Clinical practice update on bloating and distention (November 2023)

The American Gastroenterological Association (AGA) recently published best practice advice on the evaluation and management of bloating and distention [18]. The AGA Clinical Practice Update endorses serologic evaluation for celiac disease and exclusion of carbohydrate enzyme deficiencies with dietary restriction and/or breath testing, but emphasizes reserving additional evaluation with abdominal imaging and upper endoscopy for patients with alarm features, recent worsening symptoms, or an abnormal physical examination. Our approach is consistent with this guidance. (See "Overview of intestinal gas and bloating", section on 'Evaluation'.)