Citations

OBJECTIVES: Alcohol-associated liver disease is increasing, especially hospitalizations with acute on chronic liver failure and need for liver transplant. We examined trends in prevalence, inhospital mortality, and resource utilization associated with AALD and ACLF in the young. METHODS: The National Inpatient Sample (2006–2014) was queried for hospitalizations with a discharge diagnosis of cirrhosis using the International Classification of Diseases, Ninth Edition, codes. ACLF hospitalization was defined as ≥2 organ failures and stratified by age: young (≤35 years) and older (>35 years). RESULTS: Of 447,090 AALD admissions (16,126 in young) between 2006 and 2014, ACLF occurred in 29,599 (6.6%), of which 1,143 (7.1%) were in young. Compared with older, admissions in young had more women (35% vs 29%), were obese (11% vs 7.6%), were Hispanics (29% vs 18%), have alcoholic hepatitis (AH) (41% vs 17%), and have ACLF grades 2 or 3 (34% vs 25%), P < 0.001 for all. Between 2006 and 2014, ACLF in AALD among young increased from 2.8% to 5.2%, with an AH proportion from 24% to 42%, P < 0.0001 for both. Young had more complications requiring ventilation (79% vs 76%) and dialysis (32% vs 28%), P < 0.001 for both. Compared with older, ACLF admission in young had longer hospitalization (12 vs 10 days) with higher hospital charges ($127,915 vs $97,511), P < 0.0001 for both, with 20% reduced inhospital mortality (54%–45%), P < 0.001. DISCUSSION: AALD-related hospitalizations are increasing in young in the United States, mainly because of the increasing frequency of AH. Furthermore, this disease burden in young is increasing with a higher frequency of admissions with more severe ACLF and consumption of hospital resources. Studies are needed to develop preventive strategies to reduce burden related to AALD and ACLF in young.

Portal hypertensive cholangiopathy is a rare complication of extrahepatic portal vein obstruction and portal cavernoma. It is usually asymptomatic but may be associated with jaundice, biliary colic, and fever. Abdominal sonography and Doppler are ideal initial diagnostic modalities, followed by magnetic resonance cholangiopancreatography or endoscopic retrograde cholangiopancreatography. These imaging modalities are important if an intervention is planned for the management of portal hypertension and for relieving biliary obstruction. If computed tomography (CT) is performed in isolation, it may be challenging to distinguish this entity from acute on chronic portal vein thrombosis. The diagnostic results should be interpreted cautiously. This case report of an abdomen CT performed on a patient with a history of portal vein thrombosis masqueraded as an acute on chronic portal vein thrombosis with cavernous collaterals. Doppler confirmed the diagnosis of portal hypertensive cholangiopathy. Correlation with clinical symptoms and Doppler may be necessary to distinguish portal hypertensive cholangiopathy from acute portal vein thrombus.

INTRODUCTION: We present a case of idiopathic varices in the small bowel and colon discovered after extensive work up for iron-deficiency anemia and portal hypertension. CASE DESCRIPTION/METHODS: 41-year-old with no known medical history underwent esophagogastroduodenoscopy (EGD) and colonoscopy for evaluation of iron-deficiency anemia. EGD was normal. Colonoscopy revealed diffuse colonic varices extending from the cecum to the rectum (Figure 1). Computed tomography enterography showed numerous varices of the mid jejunum. Magnetic resonance imaging of the abdomen showed patent portal circulation and no other abnormalities. Echocardiogram did not show any evidence of right heart failure. Transjugular liver biopsy showed a portosytemic pressure gradient of 4 mm of Hg indicating the absence of portal hypertension. Liver biopsy only showed mild steatosis and no fibrosis. A direct measurement of portal pressure was 3 mmof Hg again indicating the absence of portal hypertension. DISCUSSION: Given the extensive workup with no evidence of portal hypertension, patient is thought have idiopathic varices in the small bowel and colon. Ectopic varices, especially in the colon are rare and are usually associated with portal hypertension. Idiopathic colonic varices in association with small bowel varices are even more infrequently described in existing literature. Clinical presentation has been reported with massive hemorrhage, recurrent bleeds and even as incidental findings in endoscopies and imaging performed for other reasons. Management options include conservative frequent follow up or surgery if there is evidence of recurrent bleeds or massive hemorrhage.

OBJECTIVES: Cardiovascular (CV) disease is the top cause of mortality in patients with nonalcoholic fatty liver disease (NAFLD). Female sex is protective against CV disease. We aimed to determine whether female sex remains a protective factor against CV disease (myocardial infarction, angina, and stroke) in NAFLD. METHODS: We identified all adults diagnosed with NAFLD in Olmsted County, Minnesota, between 1997 and 2014 and selected an age- and sex-matched (1:4) referent cohort from the general population. NAFLD was ascertained using a code-based algorithm with high validity tested by medical record review. The impact of female sex on incident CV events was examined using Cox proportional hazards regression analysis stratified by standard clinical risk factors. RESULTS: A total of 3,869 NAFLD and 15,209 age- and sex-matched referent subjects were identified. After a median follow-up time of 7 (range 1–20) years, 3,851 CV events were recorded. Female sex was protective for ischemic CV events in the general population (hazard ratio = 0.71, 95% confidence interval 0.62–0.80, P < 0.001), but the impact was significantly diminished among those with NAFLD (hazard ratio = 0.90, 95% confidence interval 0.74–1.08, P = 0.25), even after stratification by time-dependent CV risk factors and control for diagnostic testing (liver enzymes and ultrasound) during routine medical evaluations, as a surrogate of access to care. Among those with NAFLD, excess events were higher in women than in men: CV disease (18% vs 9%) and mortality (9% vs 6%). DISCUSSION: Women with NAFLD lose the CV protection conferred by the female sex, and their risk is underestimated by current estimating methods in clinical practice.

Background and Aims Among patients with cirrhosis awaiting liver transplantation, prediction of wait‐list (WL) mortality is adjudicated by the Model for End Stage Liver Disease–Sodium (MELD‐Na) score. Replacing serum creatinine (SCr) with estimated glomerular filtration rate (eGFR) in the MELD‐Na score may improve prediction of WL mortality, especially for women and highest disease severity. Approach and Results We developed (2014) and validated (2015) a model incorporating eGFR using national data (n = 17,095) to predict WL mortality. Glomerular filtration rate (GFR) was estimated using the GFR assessment in liver disease (GRAIL) developed among patients with cirrhosis. Multivariate Cox proportional hazard analysis models were used to compare the predicted 90‐day WL mortality between MELD‐GRAIL‐Na (re‐estimated bilirubin, international normalized ratio [INR], sodium, and GRAIL) versus MELD‐Na. Within 3 months, 27.8% were transplanted, 4.3% died on the WL, and 4.7% were delisted for other reasons. GFR as estimated by GRAIL (hazard ratio [HR] 0.382, 95% confidence interval [CI] 0.344‐0.424) and the re‐estimated model MELD‐GRAIL‐Na (HR 1.212, 95% CI 1.199‐1.224) were significant predictors of mortality or being delisted on the WL within 3 months. MELD‐GRAIL‐Na was a better predictor of observed mortality at highest deciles of disease severity (≥ 27‐40). For a score of 32 or higher (observed mortality 0.68), predicted mortality was 0.67 (MELD‐GRAIL‐Na) and 0.51 (MELD‐Na). For women, a score of 32 or higher (observed mortality 0.67), the predicted mortality was 0.69 (MELD‐GRAIL‐Na) and 0.55 (MELD‐Na). In 2015, use of MELD‐GRAIL‐Na as compared with MELD‐Na resulted in reclassification of 16.7% (n = 672) of patients on the WL. Conclusion Incorporation of eGFR likely captures true GFR better than SCr, especially among women. Incorporation of MELD‐GRAIL‐Na instead of MELD‐Na may affect outcomes for 12%‐17% awaiting transplant and affect organ allocation.

OBJECTIVES: Alcoholic hepatitis (AH) develops in approximately 30% of chronic heavy drinkers. The immune system of patients with AH is hyperactivated, yet ineffective against infectious diseases. Mucosal-associated invariant T (MAIT) cells are innate-like lymphocytes that are highly enriched in liver, mucosa, and peripheral blood and contribute to antimicrobial immunity. We aimed to determine whether MAIT cells were dysregulated in heavy drinkers with and without AH and the effects of alcohol abstinence on MAIT cell recovery. METHODS: MR1 tetramers loaded with a potent MAIT cell ligand 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil were used in multiparameter flow cytometry to analyze peripheral blood MAIT cells in 59 healthy controls (HC), 56 patients with AH, and 45 heavy drinkers without overt liver disease (HDC) at baseline and 6- and 12-month follow-ups. Multiplex immunoassays were used to quantify plasma levels of cytokines related to MAIT cell activation. Kinetic Turbidimetric Limulus Amebocyte Lysate Assay and ELISA were performed to measure circulating levels of 2 surrogate markers for bacterial translocation (lipopolysaccharide and CD14), respectively. RESULTS: At baseline, patients with AH had a significantly lower frequency of MAIT cells than HDC and HC. HDC also had less MAIT cells than HC (median 0.16% in AH, 0.56% in HDC, and 1.25% in HC). Further, the residual MAIT cells in patients with AH expressed higher levels of activation markers (CD69, CD38, and human leukocyte antigen [HLA]-DR), the effector molecule granzyme B, and the immune exhaustion molecule PD-1. Plasma levels of lipopolysaccharide and CD14 and several cytokines related to MAIT cell activation were elevated in patients with AH (interferon [IFN]-α, interleukin [IL]-7, IL-15, IL-17, IL-18, IL-23, IFN-γ, and tumor necrosis factor α). Decreased MAIT cell frequency and upregulated CD38, CD69, and HLA-DR correlated negatively and positively, respectively, with aspartate aminotransferase level. MAIT cell frequency negatively correlated with IL-18. HLA-DR and CD38 levels correlated with several cytokines. At follow-ups, abstinent patients with AH had increased MAIT cell frequency and decreased MAIT cell activation. However, MAIT cell frequency was not fully normalized in patients with AH (median 0.31%). DISCUSSION: We showed that HDC had a reduction of blood MAIT cells despite showing little evidence of immune activation, whereas patients with AH had a severe depletion of blood MAIT cells and the residual cells were highly activated. Alcohol abstinence partially reversed those abnormalities.

OBJECTIVES: Nosocomial infections (NIs) can be a major cause of morbidity and mortality in cirrhosis. This study aims to define the determinants of NI development and its impact on 30-day outcomes among hospitalized patients with cirrhosis. METHODS: North American Consortium for the Study of End-Stage Liver Disease enrolled patients with cirrhosis who were admitted nonelectively. Admission variables and 30-day outcomes were compared between patients with and without NI. These were also compared based on whether there was an isolated admission infection, NI, or both. Models were created for NI development using admission variables and for 30-day mortality. RESULTS: The study included 2,864 patients; of which, 15% (n = 436) developed NI. When comparing NI vs no NI, 1,866 patients were found to be infection free, whereas 562 had admission infections only, 228 had only NI, and 208 had both infections. At admission, patients with NI were more likely to be infected and have advanced cirrhosis. NIs were associated with higher rates of acute-on-chronic liver failure, death, and transplant regardless of admission infections. Patients with NI had higher respiratory infection, urinary tract infection, Clostridium difficile infection, fungal infections, and infection with vancomycin-resistant enterococci compared with patients without NI. Risk factors for NIs were admission infections, model for end-stage liver disease (MELD) > 20, systemic inflammatory response syndrome criteria, proton pump inhibitor, rifaximin, and lactulose use, but the regression model (sensitivity, 0.67; specificity, 0.63) was not robust. Age, alcohol etiology, admission MELD score, lactulose use, acute-on-chronic liver failure, acute kidney injury, intensive care unit, and NI increased the risk of death, whereas rifaximin decreased the risk of death. DISCUSSION: NIs are prevalent in hospitalized patients with cirrhosis and are associated with poor outcomes. Although higher MELD scores and systemic inflammatory response syndrome are associated with NI, all hospitalized patients with cirrhosis require vigilance and preventive strategies.

Objectives Pancreatic lesions in autosomal dominant polycystic kidney disease (ADPKD) are primarily cysts. They are increasingly recognized, with isolated reports of intraductal papillary mucinous neoplasia (IPMN). Methods Retrospective study to determine prevalence, number, size, and location of pancreatic abnormalities using abdominal magnetic resonance imaging (MRI) of genotyped ADPKD patients (seen February 1998 to October 2013) and compared with age- and sex-matched non-ADPKD controls. We evaluated presentation, investigation, and management of all IPMNs among individuals with ADPKD (January 1997 to December 2016). Results Abdominal MRIs were examined for 271 genotyped ADPKD patients. A pancreatic cyst lesion (PCL) was detected in 52 patients (19%; 95% confidence interval, 15%–23%). Thirty-seven (71%) had a solitary PCL; 15 (28%) had multiple. Pancreatic cyst lesion prevalence did not differ by genotype. Intraductal papillary mucinous neoplasia was detected in 1% of ADPKD cases. Among 12 IPMN patients (7 branch duct; 5 main duct or mixed type) monitored for about 140 months, 2 with main duct IPMNs required Whipple resection, and 1 patient died of complications from small-bowel obstruction after declining surgical intervention. Conclusions With MRI, PCLs were detected in 19% and IPMNs in 1% of 271 ADPKD patients with proven mutations, without difference across genotypes. Pancreatic cyst lesions were asymptomatic and remained stable in size.