Published online Nov 27, 2019. doi: 10.4254/wjh.v11.i11.725
Peer-review started: May 10, 2019
First decision: July 4, 2019
Revised: August 22, 2019
Accepted: October 15, 2019
Article in press: October 15, 2019
Published online: November 27, 2019
Many patients with cirrhosis report gastrointestinal (GI) symptoms such as abdominal bloating, pain, and belching. Cirrhosis has been associated with increased nitric oxide (NO) production, gut hormonal alterations, and autonomic neuropathy that can impact gastrointestinal motility. Portal hypertension has also been implicated as a potential mechanism given decreased postprandial portal blood flow resulting in congestion of the gastric wall as well as impaired antral compliance and motility. Prolonged gastric emptying has been demonstrated in 24%-95% of patients with cirrhosis and upper gastrointestinal symptoms not attributable to other causes. These usual vague upper GI symptoms have been shown to contribute significant morbidity in the cirrhotic population through malnutrition, small intestinal bacterial overgrowth, psychological distress, and reduced health related quality of life measures.
The prevalence of GI symptoms has prompted investigation into abnormalities in GI function in cirrhosis. Cirrhotic patients have higher rates of gastrointestinal dysmotility, characterized by delayed gastric emptying and prolonged small bowel transit time, compared to those without cirrhosis. While severity of cirrhosis has been associated with worsened small bowel motility, the relationship between gastric emptying and severity of liver disease has not been well established. The mechanisms for gastrointestinal dysmotility in cirrhosis are also not fully understood. Although some studies have correlated markers of portal hypertension with delayed gastric emptying, those examining the size of esophageal varices, variceal pressure, and hepatic venous pressure gradient, have failed to demonstrate an association with impaired gastric motility. Examination of the risk factors for delayed gastric emptying in patients with cirrhosis could provide further insight into the underlying pathophysiology and could help identify patients who may benefit from therapeutic interventions aimed at improving gastric motility.
The presence of retained gastric food on esophagogastroduodenoscopy (EGD) can be used as a surrogate for delayed gastric emptying with a reasonably high specificity. Since patients with cirrhosis frequently require EGD for surveillance and treatment of esophageal varices, evaluation for retained gastric food contents at EGD could provide important clinical information in this population. Therefore, we conducted this study to characterize the frequency of retained gastric food contents at EGD in a cirrhotic population compared to a control population without liver disease and to elucidate factors predictive of retained food. Specifically, we examined the relationship between retained gastric food contents with severity of cirrhosis by Child-Pugh score; and the association between retained gastric food contents with complications of decompensated cirrhosis as defined by the presence of esophageal varices, ascites, or hepatic encephalopathy.
We performed a retrospective case-control study of patients with cirrhosis who had an EGD for screening or surveillance of esophageal varices between 2000 and 2015 at an academic medical center. Patients younger than 18 years, those with intra-luminal tumor or mechanical bowel obstruction, those with a prior diagnosis of gastroparesis or prior esophageal, gastric or thoracic surgery, and those who had an EGD indication which could confound gastric emptying (food impaction, foreign body, active gastrointestinal bleed, abdominal pain, nausea, vomiting, dyspepsia, bloating, weight loss, early satiety, or post-prandial fullness) were excluded. A control group who underwent EGD for an indication of anemia was identified as anemia is unrelated to gastroparesis or its symptoms. Three hundred sixty-four patients with confirmed cirrhosis, who underwent a total of 1044 EGDs for the indication of esophageal variceal screening or surveillance, were identified. During the same period, 519 control patients without liver disease, who underwent a total of 881 EGDs for the indication of anemia, were identified. The presence of retained food on EGD was used as a surrogate for delayed gastric emptying. The relative frequency of delayed gastric emptying among cirrhotics was compared to non-cirrhotics. Characteristics of patients with and without retained food on EGD were compared using the Kruskall-Wallis test for non-parametric continuous variables and χ2 or Fisher’s exact test for categorical variables, as appropriate. A multivariable logistic regression analysis was performed including co-variates statistically significant on univariable analysis. Statistical significance was defined by a two-tailed P value of less than 0.05.
Overall, 40 (4.5%) patients had evidence of retained food on EGD. Cirrhotics were more likely to have retained food on EGD than non-cirrhotics (9.1% vs 1.4%, OR = 5.83; 95%CI: 2.32-14.7, P < 0.001). Characteristics associated with retained food on univariable analysis included age less than 60 years (12.6% vs 5.2%, P = 0.015), opioid use (P = 0.004), Child-Pugh class C (24.1% Child-Pugh class C vs 6.4% Child-Pugh class A, P = 0.007), and lower platelet count (P = 0.027). Diabetes mellitus showed a trend towards a significant association with retained food (P = 0.066). Although no complications of decompensated cirrhosis were shown to be significantly associated, the presence of esophageal varices did show a trend towards significance (P = 0.084). On multivariate logistic regression analysis, in addition to the presence of cirrhosis, diabetes mellitus (types 1 and 2 combined) (OR = 2.34; 95%CI: 1.08-5.06, P = 0.031), opioid use (OR = 3.08; 95%CI: 1.29-7.34, P = 0.011), and Child-Pugh class C (OR = 4.29; 95%CI: 1.43-12.9, P = 0.01) were also associated with a higher likelihood of food retention on EGD.
This study is the first to describe the frequency of retained gastric food contents visualized on EGD in a cirrhotic population. Our study reveals that cirrhotic patients are five times more likely to have retained food on EGD than controls. In addition, more decompensated cirrhosis was associated with a higher likelihood of gastric food contents at EGD. The factors associated with gastric retention in the study population include age younger than 60, diabetes mellitus, opioid use, thrombocytopenia, and higher Child-Pugh class. Opioid use and diabetes mellitus are well described risk factors for gastroparesis. A novel finding is the fact that gastric retention is associated with decompensated cirrhosis as can be elucidated from the association with thrombocytopenia and higher Child-Pugh class. Additionally, there was a trend towards significance with the presence of esophageal varices that further supports an association between severity of cirrhosis, portal hypertension, and gastroparesis. Prior studies evaluating the association between severity of cirrhosis and gastroparesis have shown mixed results. However, the correlation between severity of cirrhosis and delayed gastric emptying seen in this study is similar to two previous studies. Gumurdulu et al demonstrated that Child-Pugh class correlated with delayed gastric emptying, as measured by scintigraphy, and Miyajima et al concluded a similar association using measurements of autonomic function and portal blood flow via MRI. Despite the different methodologies used in those studies and the present study, the similar conclusions lend further credence to the results of the current study. Clinicians should have a higher index of suspicion for upper GI symptoms related to dysmotility in those with more decompensated cirrhosis, so that these patients can undergo timely diagnosis and treatment.
We demonstrate that cirrhotic subjects have a higher likelihood of delayed gastric emptying than non-cirrhotics, particularly in those with decompensation of their liver disease. Future studies should consider prospectively recruiting patients in multiple centers to confirm these results, though time constraints might make prospective recruitment and longitudinal follow-up difficult. Additionally, since the presence of retained food on EGD is not the gold standard method for diagnosing gastroparesis, prospective studies could utilize gastric scintigraphy, which remains the gold standard for diagnosis. Providers who care for cirrhotic patients should have a high index of suspicion for symptoms related to delayed gastric emptying, a condition which is vastly underrecognized in this patient group. Ultimately, a prospectively validated prediction tool would be useful for the detection of impaired gastric motility in cirrhotic patients. Future studies should evaluate the effect of delayed gastric emptying on patient reported outcomes, quality of life and health care utilization.