Impact of Recipient and Donor Body Mass Index on Survival Outcomes After Intestinal Transplantation: A United Network for Organ Sharing Database Analysis.

BACKGROUND Long-term patient survival after intestinal transplantation (IT) remains low compared with other organ transplants despite years of advancement in clinical experience. While patients with extremely high or low body mass index (BMI) are often considered ineligible for IT, the impact of BMI on post-transplant IT survival remains understudied. MATERIAL AND METHODS Using the United Network for Organ Sharing Standard Transplant database, we conducted a retrospective cohort study on patients who underwent IT between April 11, 1994, and September 29, 2021. We assessed the association of recipient and donor BMI at transplant with post-transplant mortality using Kaplan-Meier survival curves and univariate and multivariate Cox regression analyses. RESULTS A total of 1541 patients were included in our final sample. Of these patients, 806 were females (52.5%) and most were in the normal-weight BMI subgroup (54.2%). Obese class II (mean; 36.8±10.92 years) and underweight patients (mean; 37.6±13.37 years) were significantly younger than patients in other BMI categories. The adjusted multivariate model demonstrated an increased risk of mortality in underweight IT recipients compared to normal-weight IT recipients (aHR=1.25, 95% confidence interval [CI], 1.02-1.54; P=0.032).There was no significant association between donor BMI categories and survival in IT recipients. CONCLUSIONS Recipient BMI below normal is associated with an increased risk of mortality after intestinal transplantation and represents a potentially modifiable patient characteristic to improve survival outcomes.

Association of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) With an Increased Risk of Congestive Heart Failure in Hospitalized Patients With Cirrhosis: A Propensity Score-Matched Analysis.

INTRODUCTION: Metabolic dysfunction-associated steatotic liver disease (MASLD) is linked to increased cardiovascular (CV) risks, notably congestive heart failure (CHF). We evaluated the influence of MASLD on CHF and mortality among hospitalized cirrhotic patients. METHODS: We analyzed the National Inpatient Sample from 2016 to 2020, identifying adult cirrhosis patients. We focused on CHF and in-hospital mortality, plus hospital stay length, costs, and discharge status. Propensity score matching created balanced cohorts for comparison. Poisson and logistic regression provided adjusted CHF risks and mortality odds ratios (ORs) for MASLD patients. RESULTS: Before matching, 4.1% of 672,625 cirrhotic patients had MASLD. Post-matching, each group had 23,161 patients. Patients with MASLD showed higher CHF risk (OR 1.14, 95% CI 1.10-1.21, p<0.001) but lower in-hospital mortality (OR 0.57, 95% CI 0.52-0.63, p<0.01) and decreased costs (median $24,447 vs. $28,630, OR 0.86, 95% CI 0.85-0.87, p<0.001). CONCLUSION: In this nationwide study of patients with cirrhosis, MASLD was associated with a higher prevalence of CHF and lower in-patient mortality. These findings mirror the "adiposity paradox" phenomenon, where obese/overweight individuals with cardiometabolic dysfunction may experience less severe or beneficial health outcomes than those with a normal weight. Further investigation is warranted to decode the intricate interplay between MASLD, cirrhosis, CHF, and in-hospital mortality and its clinical practice implications.

Severe Acute Liver Injury After Hepatotoxic Medication Initiation in Real-World Data.

Importance: Current approaches to classify the hepatotoxic potential of medications are based on cumulative case reports of acute liver injury (ALI), which do not consider the size of the exposed population. There is little evidence from real-world data (data relating to patient health status and/or the delivery of health care routinely collected from sources outside of a research setting) on incidence rates of severe ALI after initiation of medications, accounting for duration of exposure. Objective: To identify the most potentially hepatotoxic medications based on real-world incidence rates of severe ALI and to examine how these rates compare with categorization based on case reports. Design, Setting, and Participants: This series of cohort studies obtained data from the US Department of Veterans Affairs on persons without preexisting liver or biliary disease who initiated a suspected hepatotoxic medication in the outpatient setting between October 1, 2000, and September 30, 2021. Data were analyzed from June 2020 to November 2023. Exposures: Outpatient initiation of any one of 194 medications with 4 or more published reports of hepatotoxicity. Main Outcomes and Measures: Hospitalization for severe ALI, defined by either inpatient: (1) alanine aminotransferase level greater than 120 U/L plus total bilirubin level greater than 2.0 mg/dL or (2) international normalized ratio of 1.5 or higher plus total bilirubin level greater than 2.0 mg/dL recorded within the first 2 days of admission. Acute or chronic liver or biliary disease diagnosis recorded during follow-up or as a discharge diagnosis of a hospitalization for severe ALI resulted in censoring. This study calculated age- and sex-adjusted incidence rates of severe ALI and compared observed rates with hepatotoxicity categories based on cumulative published case reports. Results: The study included 7 899 888 patients across 194 medication cohorts (mean [SD] age, 64.4 [16.4] years, 7 305 558 males [92.5%], 4 354 136 individuals [55.1%] had polypharmacy). Incidence rates of severe ALI ranged from 0 events per 10 000 person-years (candesartan, minocycline) to 86.4 events per 10 000 person-years (stavudine). Seven medications (stavudine, erlotinib, lenalidomide or thalidomide, chlorpromazine, metronidazole, prochlorperazine, and isoniazid) exhibited rates of 10.0 or more events per 10 000 person-years, and 10 (moxifloxacin, azathioprine, levofloxacin, clarithromycin, ketoconazole, fluconazole, captopril, amoxicillin-clavulanate, sulfamethoxazole-trimethoprim, and ciprofloxacin) had rates between 5.0 and 9.9 events per 10 000 person-years. Of these 17 medications with the highest observed rates of severe ALI, 11 (64%) were not included in the highest hepatotoxicity category when based on case reports. Conclusions and Relevance: In this study, incidence rates of severe ALI using real-world data identified the most potentially hepatotoxic medications and can serve as a tool to investigate hepatotoxicity safety signals obtained from case reports. Case report counts did not accurately reflect the observed rates of severe ALI after medication initiation.

Mortality, Hepatic Decompensation, and Cardiovascular- and Renal-Related Outcomes in Lean Versus Non-lean Patients Hospitalized With Metabolic Dysfunction-Associated Steatohepatitis (MASH).

INTRODUCTION: Metabolic dysfunction-associated steatohepatitis (MASH) is an important cause of cirrhosis and end-stage liver disease. In addition, there have been reports of worse extrahepatic outcomes, especially cardiovascular events, in patients with lean patients' fatty liver disease compared to the non-lean group. There is limited data on hepatic, cardiac, and renal outcomes in lean compared to non-lean patients with MASH. This study aims to evaluate the cardiovascular, renal, and hepatic outcomes in hospitalized US adults with MASH, focusing on a comprehensive comparison between lean and non-lean patients. METHODS: The National Inpatient Sample (NIS) database was queried from 2016 to 2020 to identify hospitalizations with MASH. Hospitalizations with a history of overweight and obesity (lean body mass index (BMI) <25 vs. lean BMI >25) were also identified. The primary outcome was in-hospital mortality. Secondary outcomes were major adverse cardiovascular outcomes (MACE: a composite of acute myocardial infarction, cardiac arrest, stroke, heart failure, and atrial fibrillation); major adverse kidney outcome (MAKE: a composite outcome of acute kidney injury (AKI), renal replacement therapy, and renal cancer), and hepatic decompensation (esophageal varices with bleeding, ascites, spontaneous bacterial peritonitis (SBP), hepatic encephalopathy, and hepatorenal syndrome) Multivariate logistic regression analysis was used to derive risk ratios for clinical outcomes. RESULTS: We included 539,275 MASH patients in our sample; 324,330 (60%) were lean. The included patients were mostly female (61%), the mean age was 64 years, and 76% were White. At baseline, non-lean patients had a higher prevalence of heart failure, hypertension, and hyperlipidemia. There was no difference in the prevalence of smoking among both groups. In a multivariate analysis, with adjustment for age, sex, race, sarcopenia, cardiometabolic risk factors, hospital characteristics, admission type, socioeconomic factors, and all comorbidities (including 31 Elixhauser comorbidities), lean status was associated with a 40% increased risk of mortality (adjusted odds ratio (aOR) 1.40, confidence interval (CI) 1.29-1.53), 19% increased risk of MACE (aOR 1.19; 95% CI 1.14-1.24), 20% increased risk of renal decompensation (aOR 1.25; 95% CI 1.20-1.30), and 33% increased risk of hepatic decompensation (aOR 1.33 CI 1.28-1.38). CONCLUSION: Lean patients with MASH are at higher risk of cardiovascular and renal outcomes and may benefit from enhanced screening for early identification and treatment to improve outcomes.

Role of ammonia and glutamine in the pathogenesis and progression of metabolic dysfunction-associated steatotic liver disease: A systematic review.

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects over 30% of the global population, with a significant risk of advancing to liver cirrhosis and hepatocellular carcinoma. The roles of ammonia and glutamine in MASLD's pathogenesis are increasingly recognized, prompting this systematic review. This systematic review was conducted through a meticulous search of literature on December 21, 2023, across five major databases, focusing on studies that addressed the relationship between ammonia or glutamine and MASLD. The quality of the included studies was evaluated using CASP checklists. This study is officially registered in the PROSPERO database (CRD42023495619) and was conducted without external funding or sponsorship. Following PRISMA guidelines, 13 studies were included in this review. The studies were conducted globally, with varying sample sizes and study designs. The appraisal indicated a mainly low bias, confirming the reliability of the evidence. Glutamine's involvement in MASLD emerged as multifaceted, with its metabolic role being critical for liver function and disease progression. Variable expressions of glutamine synthetase and glutaminase enzymes highlight metabolic complexity whereas ammonia's impact through urea cycle dysfunction suggests avenues for therapeutic intervention. However, human clinical trials are lacking. This review emphasizes the necessity of glutamine and ammonia in understanding MASLD and identifies potential therapeutic targets. The current evidence, while robust, points to the need for human studies to corroborate preclinical findings. A personalized approach to treatment, informed by metabolic differences in MASLD patients, is advocated, alongside future large-scale clinical trials for a deeper exploration into these metabolic pathways.

Cardiovascular morbidity and mortality in lean vs. non-lean MASLD: A comprehensive meta-analysis.

BACKGROUND: Lean metabolic dysfunction-associated steatotic liver disease (MASLD), characterized by a BMI < 25 kg/m² (or < 23 kg/m² in Asians), presents a challenging prognosis compared to non-lean MASLD. This study examines cardiovascular outcomes in both lean and non-lean MASLD cohorts. METHODS: In this meta-analysis, pooled odds ratios (ORs) within 95 % confidence intervals (CIs) were calculated for primary outcomes (cardiovascular mortality and major adverse cardiovascular events [MACE]) and secondary outcomes (cardiovascular disease [CVD], all-cause mortality, hypertension, and dyslipidemia). Studies comparing lean and non-lean MASLD within the same cohorts were analyzed, prioritizing those with larger sample sizes or recent publication dates. RESULTS: Twenty-one studies were identified, encompassing lean MASLD patients (n = 7153; mean age 52.9 ± 7.4; 56 % male) and non-lean MASLD patients (n = 23,514; mean age 53.2 ± 6.8; 63 % male). Lean MASLD exhibited a 50 % increase in cardiovascular mortality odds compared to non-lean MASLD (OR: 1.5, 95 % CI 1.2-1.8; p < 0.0001). MACE odds were 10 % lower in lean MASLD (OR: 0.9, 95 % CI 0.7-1.2; p = 0.7), while CVD odds were 40 % lower (p = 0.01). All-cause mortality showed a 40 % higher odds in lean MASLD versus non-lean MASLD (p = 0.06). Lean MASLD had 30 % lower odds for both hypertension (p = 0.01) and dyslipidemia (p = 0.02) compared to non-lean MASLD. CONCLUSION: Despite a favorable cardiometabolic profile and comparable MACE rates, lean individuals with MASLD face elevated cardiovascular mortality risk.

Electrocardiographic abnormalities in patients with metabolic dysfunction-associated steatotic liver disease: A systematic review and meta-analysis.

INTRODUCTION: This study review aimed to consolidate current knowledge on the electrocardiographic abnormalities observed in patients with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), formerly known as Non-Alcoholic Fatty Liver Disease (NAFLD). METHODS: This was a systematic review of studies on the association between MASLD and electrocardiographic abnormalities, published between January 1, 1946, and October 31, 2023. Data from eligible studies were extracted, analyzed, synthesized, and summarized. RESULTS: We evaluated a total of 27 studies with 8,607,500 participants overall and 1,005,101 participants with MASLD. There was a statistically significant association between MASLD and prevalent atrial fibrillation (pooled OR: 1.34 95 % CI: 1.20-1.49, p < 0.001, n = 12), shorter QRS duration (pooled SMD: -0.073, 95 % CI: -0.144 - -0.001, n = 2, p = 0.048, n = 2), QTc prolongation (p < 0.001, n = 2), LVH (pooled OR: 1.48, 95 % CI: 1.25-1.75, p < 0.001, n = 3), low voltage (p < 0.001, n = 1), ST changes (OR: 1.41, 95 % CI: 1.04-1.91, p = 0.027, n = 1), T wave inversion (p < 0.001, n = 1), axis deviation (OR: 3.21, 95 % CI: 1.99-5.17, p < 0.001, n = 1), conduction defect (OR: 2.79, 95 % CI: 1.83-4.26, p < 0.001, n = 1) and bundle branch block (OR: 2.90, 95 % CI: 1.82-4.61, p < 0.001, n = 1), any persistent heart block (p < 0.001, n = 1), fragmented QRS (p < 0.001, n = 1), and p wave dispersion (p < 0.001, n = 1) CONCLUSION: MASLD is associated with multiple ECG abnormalities which are potential markers of early cardiac involvement, highlighting the multisystemic nature of MASLD. These specific ECG abnormalities could be used in screening and management algorithms to improve cardiac risk stratification in MASLD patients. PROSPERO REGISTRATION: CRD42023477501.

An explainable machine learning model for prediction of high-risk nonalcoholic steatohepatitis.

Early identification of high-risk metabolic dysfunction-associated steatohepatitis (MASH) can offer patients access to novel therapeutic options and potentially decrease the risk of progression to cirrhosis. This study aimed to develop an explainable machine learning model for high-risk MASH prediction and compare its performance with well-established biomarkers. Data were derived from the National Health and Nutrition Examination Surveys (NHANES) 2017-March 2020, which included a total of 5281 adults with valid elastography measurements. We used a FAST score ≥ 0.35, calculated using liver stiffness measurement and controlled attenuation parameter values and aspartate aminotransferase levels, to identify individuals with high-risk MASH. We developed an ensemble-based machine learning XGBoost model to detect high-risk MASH and explored the model's interpretability using an explainable artificial intelligence SHAP method. The prevalence of high-risk MASH was 6.9%. Our XGBoost model achieved a high level of sensitivity (0.82), specificity (0.91), accuracy (0.90), and AUC (0.95) for identifying high-risk MASH. Our model demonstrated a superior ability to predict high-risk MASH vs. FIB-4, APRI, BARD, and MASLD fibrosis scores (AUC of 0.95 vs. 0.50, 0.50, 0.49 and 0.50, respectively). To explain the high performance of our model, we found that the top 5 predictors of high-risk MASH were ALT, GGT, platelet count, waist circumference, and age. We used an explainable ML approach to develop a clinically applicable model that outperforms commonly used clinical risk indices and could increase the identification of high-risk MASH patients in resource-limited settings.

Genetic and epigenetic determinants of non-alcoholic fatty liver disease (NAFLD) in lean individuals: a systematic review.

Background: Non-alcoholic fatty liver disease (NAFLD) is common in obese individuals, but its occurrence in lean individuals and the underlying mechanisms are not well understood. This study aimed to systematically review the literature on the genetic and epigenetic factors influencing NAFLD in lean individuals. Methods: A comprehensive search was conducted on April 2nd, 2023, in seven databases using specific criteria. Only peer-reviewed studies in English, focusing on genetic or epigenetic effects on NAFLD in lean individuals, were included for qualitative synthesis. The Newcastle Ottawa Scale (NOS) was used for quality assessment. This study is registered with PROSPERO (CRD42023413809). Results: Following PRISMA guidelines, 18 studies were included in this review. The studies were conducted globally, with varying sample sizes and study designs. The NOS quality assessment revealed a moderate overall quality with variations in risk of bias and limitations in comparability and ascertainments of exposure among contributing studies. Genetic determinants related to lipid metabolism, inflammation, and oxidative stress pathways were identified, including PNPLA3 and TM6SF2 gene variants associated with increased NAFLD risk in lean individuals. Epigenetic modifications, particularly depletion of histone variants, were also implicated. However, some studies found no significant associations between genetic or clinical characteristics and lean NAFLD. Less frequent genetic risk factors, such as CETP and APOC3 gene variants, were reported. Conclusions: This systematic review underscores the importance of investigating genetic and epigenetic factors in lean NAFLD. The findings highlight the role of PNPLA3 and TM6SF2 gene variants and suggest potential epigenetic contributions. Further research is needed to fully understand the genetic and epigenetic mechanisms underlying NAFLD in lean individuals.

Clinical and Histopathological Discoveries in Patients with Hepatic Injury and Cholangiopathy Who Have Died of COVID-19: Insights and Opportunities for Intervention.

The COVID-19 pandemic has had a profound impact on global health, necessitating a comprehensive understanding of its diverse manifestations. Cholangiopathy, a condition characterized by biliary dysfunction, has emerged as a significant complication in COVID-19 patients. In this review, we report the epidemiology of COVID-19, describe the hepatotropism of SARS-CoV-2, and present the histopathology of acute liver injury (ALI) in COVID-19. Additionally, we explore the relationship between pre-existing chronic liver disease and COVID-19, shedding light on the increased susceptibility of these individuals to develop cholangiopathy. Through an in-depth analysis of cholangiopathy in COVID-19 patients, we elucidate its clinical manifestations, diagnostic criteria, and underlying pathogenesis involving inflammation, immune dysregulation, and vascular changes. Furthermore, we provide a summary of studies investigating post-COVID-19 cholangiopathy, highlighting the long-term effects and potential management strategies for this condition, and discussing opportunities for intervention, including therapeutic targets, diagnostic advancements, supportive care, and future research needs.

Artificial intelligence in endoscopic imaging for detection of malignant biliary strictures and cholangiocarcinoma: a systematic review.

Background: Artificial intelligence (AI), when applied to computer vision using a convolutional neural network (CNN), is a promising tool in "difficult-to-diagnose" conditions such as malignant biliary strictures and cholangiocarcinoma (CCA). The aim of this systematic review is to summarize and review the available data on the diagnostic utility of endoscopic AI-based imaging for malignant biliary strictures and CCA. Methods: In this systematic review, PubMed, Scopus and Web of Science databases were reviewed for studies published from January 2000 to June 2022. Extracted data included type of endoscopic imaging modality, AI classifiers, and performance measures. Results: The search yielded 5 studies involving 1465 patients. Of the 5 included studies, 4 (n=934; 3,775,819 images) used CNN in combination with cholangioscopy, while one study (n=531; 13,210 images) used CNN with endoscopic ultrasound (EUS). The average image processing speed of CNN with cholangioscopy was 7-15 msec per frame while that of CNN with EUS was 200-300 msec per frame. The highest performance metrics were observed with CNN-cholangioscopy (accuracy 94.9%, sensitivity 94.7%, and specificity 92.1%). CNN-EUS was associated with the greatest clinical performance application, providing station recognition and bile duct segmentation; thus reducing procedure length and providing real-time feedback to the endoscopist. Conclusions: Our results suggest that there is increasing evidence to support a role for AI in the diagnosis of malignant biliary strictures and CCA. CNN-based machine leaning of cholangioscopy images appears to be the most promising, while CNN-EUS has the best clinical performance application.

Artificial intelligence in medical imaging for cholangiocarcinoma diagnosis: A systematic review with scientometric analysis.

INTRODUCTION: Artificial intelligence (AI), by means of computer vision in machine learning, is a promising tool for cholangiocarcinoma (CCA) diagnosis. The aim of this study was to provide a comprehensive overview of AI in medical imaging for CCA diagnosis. METHODS: A systematic review with scientometric analysis was conducted to analyze and visualize the state-of-the-art of medical imaging to diagnosis CCA. RESULTS: Fifty relevant articles, published by 232 authors and affiliated with 68 organizations and 10 countries, were reviewed in depth. The country with the highest number of publications was China, followed by the United States. Collaboration was noted for 51 (22.0%) of the 232 authors forming five clusters. Deep learning algorithms with convolutional neural networks (CNN) were the most frequently used classifiers. The highest performance metrics were observed with CNN-cholangioscopy for diagnosis of extrahepatic CCA (accuracy 94.9%; sensitivity 94.7%; and specificity 92.1%). However, some of the values for CNN in CT imaging for diagnosis of intrahepatic CCA were low (AUC 0.72 and sensitivity 44%). CONCLUSION: Our results suggest that there is increasing evidence to support the role of AI in the diagnosis of CCA. CNN-based computer vision of cholangioscopy images appears to be the most promising modality for extrahepatic CCA diagnosis. Our social network analysis highlighted an Asian and American predominance in the research relational network of AI in CCA diagnosis. This discrepancy presents an opportunity for coordination and increased collaboration, especially with institutions located in high CCA burdened countries.

The Application of Artificial Intelligence (AI)-Based Ultrasound for the Diagnosis of Fatty Liver Disease: A Systematic Review.

Fatty liver disease, also known as hepatic steatosis, poses a significant global health concern due to the excessive accumulation of fat within the liver. If left untreated, this condition can give rise to severe complications. Recent advances in artificial intelligence (AI, specifically AI-based ultrasound imaging) offer promising tools for diagnosing this condition. This review endeavors to explore the current state of research concerning AI's role in diagnosing fatty liver disease, with a particular emphasis on imaging methods. To this end, a comprehensive search was conducted across electronic databases, including Google Scholar and Embase, to identify relevant studies published between January 2010 and May 2023, with keywords such as "fatty liver disease" and "artificial intelligence (AI)." The article selection process adhered to the PRISMA framework, ultimately resulting in the inclusion of 13 studies. These studies leveraged AI-assisted ultrasound due to its accessibility and cost-effectiveness, and they hailed from diverse countries, including India, China, Singapore, the United States, Egypt, Iran, Poland, Malaysia, and Korea. These studies employed a variety of AI classifiers, such as support vector machines, convolutional neural networks, multilayer perceptron, fuzzy Sugeno, and probabilistic neural networks, all of which demonstrated a remarkable level of precision. Notably, one study even achieved a diagnostic accuracy rate of 100%, underscoring AI's potential in diagnosing fatty liver disease. Nevertheless, the review acknowledged certain limitations within the included studies, with the majority featuring relatively small sample sizes, often encompassing fewer than 100 patients. Additionally, the variability in AI algorithms and imaging techniques added complexity to the comparative analysis. In conclusion, this review emphasizes the potential of AI in enhancing the diagnosis and management of fatty liver disease through advanced imaging techniques. Future research endeavors should prioritize the execution of large-scale studies that employ standardized AI algorithms and imaging techniques to validate AI's utility in diagnosing this prevalent health condition.

Chronic opioid use is associated with obstructive and spastic disorders in the esophagus.

BACKGROUND AND AIMS: Chronic opioid effects on the esophagus are poorly understood. We investigated whether opioids were associated with increased prevalence of esophageal motility disorders. METHODS: A retrospective study of all patients undergoing high-resolution manometry (HREM) at the Yale Gastrointestinal Motility Lab between January 2014 and August 2019. Data were extracted from the electronic medical record after studies were reviewed by two motility specialists using the Chicago Classification v.3.0. We compared the manometric results of patients who use opioids to those who do not and adjusted for type and dose of opioids using a 24 h Morphine Milligram Equivalents (MME) scale to compare patients taking low or high amounts of opioids. RESULTS: Four manometric abnormalities were significantly different between the opioid and non-opioid users. Achalasia type III, esophagogastric junction outflow obstruction (EGJOO), and distal esophageal spasm (DES) (p < 0.005, p < 0.01, and p < 0.005, respectively) were common among opioid users, whereas ineffective esophageal motility (IEM) was more common among non-opioid users (p < 0.01). The incidence of EGJOO was significantly higher in opioid users compared to non-opioid users (p < 0.001). Lastly, IRP, DCI, and distal latency were significantly different between the two groups. Patients in the high MME group had significantly greater IRP, DCI, and lower distal latency than non-opioids (p < 0.001). Also, achalasia type III and DES were more common in the high but not the low MME group. CONCLUSIONS: Opioid use is associated with multiple abnormalities on esophageal motility and these effects may be dose-dependent.

Treatment and prevention of viral hepatitis in pregnancy.

Viral hepatitis in pregnancy may be caused by many types of viruses that cause systemic infection or target hepatocytes in their pathogenesis. Because viral hepatitis during pregnancy may represent acute or chronic infection or the reactivation of a prior infection, a high clinical suspicion, medical history review, and awareness of risk factors for the acquisition of infection are important management principles. The route of infection varies widely and ranges from fecal-oral transmission for the hepatitis A and E viruses to vertical transmission for hepatitis B, blood-borne transmission for hepatitis C, and sexual transmission for the herpes simplex virus. For this reason, the exposure details about travel, food preferences, drug use, and sexual contacts are important to elicit. Although routine prenatal screening is recommended for chronic viral hepatitis caused by hepatitis B and C, most other causes of viral hepatitis in pregnancy are detected in the setting of compatible signs and symptoms (fatigue, abdominal discomfort, jaundice, scleral icterus) or incidentally noted transaminitis on routine labs. Serologic testing is helpful for diagnosis with molecular testing as indicated to guide the management of hepatitis B and C. Preventive vaccines for hepatitis A and B with established safety of use in pregnancy are recommended for women who are at risk of acquisition. Postexposure prophylaxis for hepatitis A is a single dose of immunoglobulin and vaccination can be used if immunoglobulin G is not available. Antiviral therapy with tenofovir disoproxil fumarate is recommended as prophylaxis in pregnant women with active hepatitis B and an elevated viral load (>200,000 IU/mL) during the third trimester to prevent vertical transmission. The neonate exposed to hepatitis B at birth should receive immunoglobulin G and a monovalent birth dose vaccine within 12 hours, followed by completion of the 3-dosage vaccine series. The prevalence of hepatitis C in women of reproductive age has increased in the United States, and the role of antiviral therapy during pregnancy is of great interest. Cesarean delivery is not currently recommended for the sole purpose of reducing vertical transmission risk in pregnant women with viral hepatitis. Breastfeeding is recommended in women with hepatitis A, B, and C. New and promising prevention and treatment options for hepatitis B and C are under investigation. Investigators and regulatory authorities should ensure that these clinical trials for promising antivirals and vaccines are designed to include pregnant and lactating women.

Role of Prophylactic Cholecystectomy After Endoscopic Sphincterotomy for Biliary Stone Disease: A Systematic Review and Meta-analysis.

OBJECTIVE: The aim of this study was to perform a structured systematic review and meta-analysis to evaluate the effectiveness and complication rate of cholecystectomy deferral versus prophylactic cholecystectomy among patients post-endoscopic biliary sphincterotomy for common bile duct stones. BACKGROUND: Although previous reports suggest a decreased risk of biliary complications with prophylactic cholecystectomy, biliary endoscopic cholangiopancreatography (ERCP) with sphincterotomy may provide a role for deferring cholecystectomy with the gallbladder left in situ. METHODS: Searches of PubMed, EMBASE, Web of Science, and Cochrane Library databases were performed through August 2019 in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-Analysis of Observational Studies in Epidemiology guidelines. Measured outcomes included: mortality, recurrent biliary pain or cholecystitis, pancreatitis, cholangitis, and eventual need for cholecystectomy. Random effects models were used to determine pooled effect size and corresponding 95% confidence intervals (CIs). RESULTS: Nine studies (n = 1605) were included. A total of 53.8% (n = 864) patients had deferred cholecystectomy post-sphincterotomy. Deferral cholecystectomy as compared to prophylactic cholecystectomy resulted in a significant increased risk of mortality [odds raio (OR) 2.56 (95% confidence interval, CI 1.54-4.23); P < 0.0001; I2 = 18.49]. Patients who did not undergo prophylactic cholecystectomy developed more recurrent biliary pain or cholecystitis [OR 5.10 (95% CI 3.39-7.67); P < 0.0001; I2 = 0.00]. Rate of pancreatitis [OR 3.11 (95% CI 0.99-9.83); P = 0.053; I2 = 0.00] and cholangitis [OR 1.49 (95% CI 0.74-2.98); P = 0.264; I2 = 0.00] was unaffected. Overall, 26.00% (95% CI 14.00-40.00) of patients with deferred prophylactic cholecystectomy required eventual cholecystectomy. CONCLUSIONS: Prophylactic cholecystectomy remains the preferred strategy compared to a deferral approach with gallbladder in situ post-sphincterotomy for patients with bile duct stones. Future studies may highlight a subset of patients (ie, those with large balloon biliary dilation) that may not require cholecystectomy.