AGA Clinical Practice Update on Pregnancy-Related Gastrointestinal and Liver Disease: Expert Review.

DESCRIPTION: The purpose of this American Gastroenterological Association (AGA) Institute Clinical Practice Update is to review the available published evidence and expert advice regarding the clinical management of patients with pregnancy-related gastrointestinal and liver disease. METHODS: This expert review was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the Clinical Practice Updates Committee and external peer review through the standard procedures of Gastroenterology. This article provides practical advice for the management of pregnant patients with gastrointestinal and liver disease based on the best available published evidence. The Best Practice Advice statements were drawn from a review of the published literature and from expert opinion. Because formal systematic reviews were not performed, these Best Practice Advice statements do not carry formal ratings regarding the quality of evidence or strength of the presented considerations. Best Practice Advice Statements BEST PRACTICE ADVICE 1: To optimize gastrointestinal and liver disease before pregnancy, preconception and contraceptive care counseling by a multidisciplinary team should be encouraged for reproductive-aged persons who desire to become pregnant. BEST PRACTICE ADVICE 2: Procedures, medications, and other interventions to optimize maternal health should not be withheld solely because a patient is pregnant and should be individualized after an assessment of the risks and benefits. BEST PRACTICE ADVICE 3: Coordination of birth for a pregnant patient with complex inflammatory bowel disease, advanced cirrhosis, or a liver transplant should be managed by a multidisciplinary team, preferably in a tertiary care center. BEST PRACTICE ADVICE 4: Early treatment of nausea and vomiting of pregnancy may reduce progression to hyperemesis gravidarum. In addition to standard diet and lifestyle measures, stepwise treatment consists of symptom control with vitamin B6 and doxylamine, hydration, and adequate nutrition; ondansetron, metoclopramide, promethazine, and intravenous glucocorticoids may be required in moderate to severe cases. BEST PRACTICE ADVICE 5: Constipation in pregnant persons may result from hormonal, medication-related, and physiological changes. Treatment options include dietary fiber, lactulose, and polyethylene glycol-based laxatives. BEST PRACTICE ADVICE 6: Elective endoscopic procedures should be deferred until the postpartum period, whereas nonemergent but necessary procedures should ideally be performed in the second trimester. Pregnant patients with cirrhosis should undergo evaluation for, and treatment of, esophageal varices; upper endoscopy is suggested in the second trimester (if not performed within 1 year before conception) to guide consideration of nonselective ß-blocker therapy or endoscopic variceal ligation. BEST PRACTICE ADVICE 7: In patients with inflammatory bowel disease, clinical remission before conception, during pregnancy, and in the postpartum period is essential for improving outcomes of pregnancy. Biologic agents should be continued throughout pregnancy and the postpartum period; use of methotrexate, thalidomide, and ozanimod must be stopped at least 6 months before conception. BEST PRACTICE ADVICE 8: Endoscopic retrograde cholangiopancreatography during pregnancy may be performed for urgent indications, such as choledocholithiasis, cholangitis, and some cases of gallstone pancreatitis. Ideally, endoscopic retrograde cholangiopancreatography should be performed during the second trimester, but if deferring the procedure may be detrimental to the health of the patient and fetus, a multidisciplinary team should be convened to decide on the advisability of endoscopic retrograde cholangiopancreatography. BEST PRACTICE ADVICE 9: Cholecystectomy is safe during pregnancy; a laparoscopic approach is the standard of care regardless of trimester, but ideally in the second trimester. BEST PRACTICE ADVICE 10: The diagnosis of intrahepatic cholestasis of pregnancy is based on a serum bile acid level >10 µmol/L in the setting of pruritus, typically during the second or third trimester. Treatment should be offered with oral ursodeoxycholic acid in a total daily dose of 10-15 mg/kg. BEST PRACTICE ADVICE 11: Management of liver diseases unique to pregnancy, such as pre-eclampsia; hemolysis, elevated liver enzymes, and low platelets syndrome; and acute fatty liver of pregnancy requires planning for delivery and timely evaluation for possible liver transplantation. Daily aspirin prophylaxis for patients at risk for pre-eclampsia or hemolysis, elevated liver enzymes, and low platelets syndrome is advised beginning at week 12 of gestation. BEST PRACTICE ADVICE 12: In patients with chronic hepatitis B virus infection, serum hepatitis B virus DNA and liver biochemical test levels should be ordered. Patients not on treatment but with a serum hepatitis B virus DNA level >200,000 IU/mL during the third trimester of pregnancy should be considered for treatment with tenofovir disoproxil fumarate. BEST PRACTICE ADVICE 13: In patients on immunosuppressive therapy for chronic liver diseases or after liver transplantation, therapy should be continued at the lowest effective dose during pregnancy. Mycophenolate mofetil should not be administered during pregnancy.

An artificial intelligence-generated model predicts 90-day survival in alcohol-associated hepatitis: A global cohort study.

BACKGROUND AND AIMS: Alcohol-associated hepatitis (AH) poses significant short-term mortality. Existing prognostic models lack precision for 90-day mortality. Utilizing artificial intelligence in a global cohort, we sought to derive and validate an enhanced prognostic model. APPROACH AND RESULTS: The Global AlcHep initiative, a retrospective study across 23 centers in 12 countries, enrolled patients with AH per National Institute for Alcohol Abuse and Alcoholism criteria. Centers were partitioned into derivation (11 centers, 860 patients) and validation cohorts (12 centers, 859 patients). Focusing on 30 and 90-day postadmission mortality, 3 artificial intelligence algorithms (Random Forest, Gradient Boosting Machines, and eXtreme Gradient Boosting) informed an ensemble model, subsequently refined through Bayesian updating, integrating the derivation cohort's average 90-day mortality with each center's approximate mortality rate to produce posttest probabilities. The ALCoholic Hepatitis Artificial INtelligence Ensemble score integrated age, gender, cirrhosis, and 9 laboratory values, with center-specific mortality rates. Mortality was 18.7% (30 d) and 27.9% (90 d) in the derivation cohort versus 21.7% and 32.5% in the validation cohort. Validation cohort 30 and 90-day AUCs were 0.811 (0.779-0.844) and 0.799 (0.769-0.830), significantly surpassing legacy models like Maddrey's Discriminant Function, Model for End-Stage Liver Disease variations, age-serum bilirubin-international normalized ratio-serum Creatinine score, Glasgow, and modified Glasgow Scores ( p < 0.001). ALCoholic Hepatitis Artificial INtelligence Ensemble score also showcased superior calibration against MELD and its variants. Steroid use improved 30-day survival for those with an ALCoholic Hepatitis Artificial INtelligence Ensemble score > 0.20 in both derivation and validation cohorts. CONCLUSIONS: Harnessing artificial intelligence within a global consortium, we pioneered a scoring system excelling over traditional models for 30 and 90-day AH mortality predictions. Beneficial for clinical trials, steroid therapy, and transplant indications, it's accessible at: https://aihepatology.shinyapps.io/ALCHAIN/ .

Evolutionary changes in metabolic dysfunction-associated steatotic liver disease and risk of hepatocellular carcinoma: A nationwide cohort study.

BACKGROUND/AIMS: To determine the association between evolutionary changes in metabolic dysfunction-associated steatotic liver disease (MASLD) status and the risk of hepatocellular carcinoma (HCC) in a nationwide population-based cohort. METHODS: Information on study participants was derived from the Korea National Health Insurance Service database. The study population consisted of 5,080,410 participants who underwent two consecutive biennial health screenings between 2009 and 2012. All participants were followed up until HCC, death, or 31 December 2020. The association of evolutionary changes in MASLD status, as assessed by the fatty liver index and cardiometabolic risk factors, including persistent non-MASLD, resolved MASLD, incident MASLD, and persistent MASLD, with HCC risk was evaluated using multivariable-adjusted Cox proportional hazards regression. RESULTS: Among the 5,080,410 participants with 39,910,331 person-years of follow-up, 4,801 participants developed HCC. The incidence of HCC in participants with resolved, incident, and persistent MASLD was approximately 2.2-, 2.3-, and 4.7-fold higher, respectively, than that in those with persistent non-MASLD among the Korean adult population. When stratifying the participants according to the evolutionary change in MASLD status, persistent (adjusted hazard ratio [aHR], 2.94; 95% confidence interval [CI], 2.68-3.21; P<0.001), incident (aHR, 1.85; 95% CI, 1.63-2.10; P<0.001), and resolved MASLD (aHR, 1.33; 95% CI, 1.18-1.50; P<0.001) had an increased risk of HCC compared to persistent non-MASLD. CONCLUSION: The evolutionary changes in MASLD were associated with the differential risk of HCC independent of metabolic risk factors and concomitant medications, providing additional information on the risk of HCC stratification in patients with MASLD.

Antibiotic exposure and depression incidence: A cohort study of the Korean population.

Recent research highlights the crucial role of the gut-brain axis in understanding depression etiologies. While burgeoning studies suggest an association between disruptions in gut microbiota and the development of depression, limited longitudinal studies have investigated this link. To address this gap, we conducted a retrospective cohort study using National Health Insurance Service-Health Screening Cohort (NHIS-HEALS) data in South Korea, involving 199,144 individuals aged 40-79. We examined the impact of cumulative antibiotic exposure (2004-2008) on subsequent depression incidence (2009-2013) by conducting Cox proportional hazards regressions. Our findings show an increasing depression risk with extended antibiotic exposure after adjusting for comorbidities and behavioral covariates. A broader antibiotic spectrum was associated with a higher depression risk. These trends persisted after adjusting for the original antibiotic indications. In conclusion, our study highlights the duration-dependent association between antibiotic exposure and increased depression risk, offering insights into depression etiologies and relevant novel therapeutic tools, and advocating for heightened antibiotic stewardship considering their impact on mental health.

Associations of cholecystectomy with metabolic health changes and incident cardiovascular disease: a retrospective cohort study.

Although some studies conducted about the risk of cholecystectomy and cardiovascular disease, there was a limit to explaining the relationship. We investigated the short-term and long-term relationship between cholecystectomy and cardiovascular disease, and evidence using the elements of the metabolic index as an intermediate step. It was a retrospective cohort study and we used the National Health Insurance Service database of South Korea between 2002 and 2015. Finally, 5,210 patients who underwent cholecystectomy and 49,457 at 1:10 age and gender-matched controls of subjects were collected. The main results was estimated by Multivariate Cox proportional hazard regression to calculate the hazard ratio (HR) with 95% confidence interval (CI) for risk of cardiovascular disease after cholecystectomy. Regarding short-term effects of cholecystectomy, increased risk of cardiovascular disease (aHR 1.35, 95% CI 1.15-1.58) and coronary heart disease (aHR 1.77, 95% CI 1.44-2.16) were similarly seen within 2 years of surgery. When analyzing the change in metabolic risk factors, cholecystectomy was associated with a change in systolic blood pressure (adjusted mean [aMean]: 1.51, 95% CI: [- 1.50 to - 4.51]), total cholesterol (aMean - 14.14, [- 20.33 to 7.95]) and body mass index (aMean - 0.13, [- 0.37 to 0.11]). Cholecystectomy patients had elevated risk of cardiovascular disease in the short-term, possibly due to the characteristics of the patient before surgery. The association of cholecystectomy and cardiovascular disease has decreased after 2 years in patients who underwent cholecystectomy, suggesting that because of improvement of metabolic health, cholecystectomy-associated elevation of cardiovascular disease risk may be ameliorated 2 years after cholecystectomy.

African American race does not confer an increased risk of clinical events in patients with primary sclerosing cholangitis.

BACKGROUND: The natural history of primary sclerosing cholangitis (PSC) among African Americans (AA) is not well understood. METHODS: Transplant-free survival and hepatic decompensation-free survival were assessed using a retrospective research registry from 16 centers throughout North America. Patients with PSC alive without liver transplantation after 2008 were included. Diagnostic delay was defined from the first abnormal liver test to the first abnormal cholangiogram/liver biopsy. Socioeconomic status was imputed by the Zip code. RESULTS: Among 850 patients, 661 (77.8%) were non-Hispanic Whites (NHWs), and 85 (10.0%) were AA. There were no significant differences by race in age at diagnosis, sex, or PSC type. Inflammatory bowel disease was more common in NHWs (75.8% vs. 51.8% p=0.0001). The baseline (median, IQR) Amsterdam-Oxford Model score was lower in NHWs (14.3, 13.4-15.2 vs. 15.1, 14.1-15.7, p=0.002), but Mayo risk score (0.03, -0.8 to 1.1 vs. 0.02, -0.7 to 1.0, p=0.83), Model for End-stage Liver Disease (5.9, 2.8-10.7 vs. 6.4, 2.6-10.4, p=0.95), and cirrhosis (27.4% vs. 27.1%, p=0.95) did not differ. Race was not associated with hepatic decompensation, and after adjusting for clinical variables, neither race nor socioeconomic status was associated with transplant-free survival. Variables independently associated with death/liver transplant (HR, 95% CI) included age at diagnosis (1.04, 1.02-1.06, p<0.0001), total bilirubin (1.06, 1.04-1.08, p<0.0001), and albumin (0.44, 0.33-0.61, p<0.0001). AA race did not affect the performance of prognostic models. CONCLUSIONS: AA patients with PSC have a lower rate of inflammatory bowel disease but similar progression to hepatic decompensation and liver transplant/death compared to NHWs.

ACG Clinical Guideline: disorders of the hepatic and mesenteric circulation

Disorders of the mesenteric, portal, and hepatic veins and mesenteric and hepatic arteries have important clinical consequences and may lead to acute liver failure, chronic liver disease, noncirrhotic portal hypertension, cirrhosis, and hepatocellular carcinoma. Although literature in the field of vascular liver disorders is scant, these disorders are common in clinical practice, and general practitioners, gastroenterologists, and hepatologists may benefit from expert guidance and recommendations for management of these conditions. These guidelines represent the official practice recommendations of the American College of Gastroenterology. Key concept statements based on author expert opinion and review of literature and specific recommendations based on PICO/GRADE analysis have been developed to aid in the management of vascular liver disorders. These recommendations and guidelines should be tailored to individual patients and circumstances in routine clinical practice.