Bile Acid Profiles in Primary Sclerosing Cholangitis and Their Ability to Predict Hepatic Decompensation.

BACKGROUND AND AIMS: Altered bile acid (BA) homeostasis is an intrinsic facet of cholestatic liver diseases, but clinical usefulness of plasma BA assessment in primary sclerosing cholangitis (PSC) remains understudied. We performed BA profiling in a large retrospective cohort of patients with PSC and matched healthy controls, hypothesizing that plasma BA profiles vary among patients and have clinical utility. APPROACH AND RESULTS: Plasma BA profiling was performed in the Clinical Biochemical Genetics Laboratory at Mayo Clinic using a mass spectrometry based assay. Cox proportional hazard (univariate) and gradient boosting machines (multivariable) models were used to evaluate whether BA variables predict 5-year risk of hepatic decompensation (HD; defined as ascites, variceal hemorrhage, or encephalopathy). There were 400 patients with PSC and 302 controls in the derivation cohort (Mayo Clinic) and 108 patients with PSC in the validation cohort (Norwegian PSC Research Center). Patients with PSC had increased BA levels, conjugated fraction, and primary-to-secondary BA ratios relative to controls. Ursodeoxycholic acid (UDCA) increased total plasma BA level while lowering cholic acid and chenodeoxycholic acid concentrations. Patients without inflammatory bowel disease (IBD) had primary-to-secondary BA ratios between those of controls and patients with ulcerative colitis. HD risk was associated with increased concentration and conjugated fraction of many BA, whereas higher G:T conjugation ratios were protective. The machine-learning model, PSC-BA profile score (concordance statistic [C-statistic], 0.95), predicted HD better than individual measures, including alkaline phosphatase, and performed well in validation (C-statistic, 0.86). CONCLUSIONS: Patients with PSC demonstrated alterations of plasma BA consistent with known mechanisms of cholestasis, UDCA treatment, and IBD. Notably, BA profiles predicted future HD, establishing the clinical potential of BA profiling, which may be suited for use in clinical trials.

Liver transplantation for acute liver failure in a SARS-CoV-2 PCR-positive patient.

Current guidelines recommend deferring liver transplantation (LT) in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection until clinical improvement occurs and two PCR tests collected at least 24 hours apart are negative. We report a case of an 18-year-old, previously healthy African-American woman diagnosed with COVID-19, who presents with acute liver failure (ALF) requiring urgent LT in the context of SARS-CoV-2 polymerase chain reaction (PCR) positivity. The patient was thought to have acute Wilsonian crisis on the basis of hemolytic anemia, alkaline phosphatase:bilirubin ratio <4, AST:ALT ratio >2.2, elevated serum copper, and low uric acid, although an unusual presentation of COVID-19 causing ALF could not be excluded. After meeting criteria for status 1a listing, the patient underwent successful LT, despite ongoing SARS-CoV-2 PCR positivity. Remdesivir was given immediately posttransplant, and mycophenolate mofetil was withheld initially and the SARS-CoV-2 PCR test eventually became negative. Three months following transplantation, the patient has made a near-complete recovery. This case highlights that COVID-19 with SARS-CoV-2 PCR positivity may not be an absolute contraindication for transplantation in ALF. Criteria for patient selection and timing of LT amid the COVID-19 pandemic need to be validated in future studies.

Impact of topical budesonide on prevention of esophageal stricture after mucosal resection.

BACKGROUND AND AIMS: EMR and endoscopic submucosal dissection (ESD) are treatment modalities for Barrett's esophagus involving high-grade dysplasia or early cancer. Injectional corticosteroid therapy decreases the risk of procedure-related esophageal stricture (ES) formation. Our aim was to assess the efficacy of topical budesonide on the rate of ES formation after EMR or ESD. METHODS: Patients included prospectively from 3 tertiary endoscopy centers received 3 mg budesonide orally twice a day for 8 weeks after esophageal EMR or ESD of 50% or more of the esophageal circumference between January 1, 2014 and June 30, 2018. These patients were matched (1:3 ratio) retrospectively with a consecutive patient cohort who underwent EMR or ESD of 50% or more of the esophageal circumference without concomitant corticosteroid therapy. The primary endpoint was the presence of ES at the 12-week follow-up. RESULTS: Twenty-five patients (budesonide) were matched with 75 patients (no budesonide). Most underwent EMR for Barrett's esophagus with biopsy-proven high-grade dysplasia or suspected T1a cancer. Although most baseline characteristics did not differ significantly, patients in the budesonide cohort tended to have a higher proportion of circumferential EMR. The proportion of patients with ES was not significantly lower in the budesonide cohort (16% vs 28%). On logistic regression analysis, budesonide remained associated with a lower incidence of ES (P = .023); however, when controlling for baseline characteristics with a propensity score weighted logistic regression model, there was no significant effect on ES formation (P = .176). CONCLUSIONS: Topical budesonide might be associated with a reduction of ES after EMR or ESD; however, further studies are needed to verify our results.

Evolving Role of Liver Transplantation in Elderly Recipients.

The need for liver transplantation (LT) among older patients is increasing, but the role of LT in the elderly (≥70 years) is not well defined. We retrospectively reviewed all primary LTs from 1998 through 2016 at our center. Survival and associated risk factors were analyzed with Cox regression and Kaplan-Meier methods for LT recipients in 3 age groups: <60, 60-69, and ≥70 years. Among 2281 LT recipients, the median age was 56 years (range, 15-80 years), and 162 were aged ≥70 years. The estimated 5- and 10-year patient survival probabilities for elderly LT recipients were lower (70.8% and 43.6%) than for recipients aged 60-69 years (77.2% and 64.6%) and <60 years (80.7% and 67.6%). Patient and graft survival rates associated with LT improved over time from the pre-Model for End-Stage Liver Disease era to Share 15, pre-Share 35, and Share 35 for the cohort overall (P < 0.001), but rates remained relatively stable in septuagenarians throughout the study periods (all P > 0.45). There was no incremental negative effect of age at LT among elderly patients aged 70-75 years (log-rank P = 0.32). Among elderly LT recipients, greater requirement for packed red blood cells and longer warm ischemia times were significantly associated with decreased survival (P < 0.05). Survival of LT recipients, regardless of age, markedly surpassed that of patients who were denied LT, but it was persistently 20%-30% lower than the expected survival of the general US population (P < 0.001). With the aging of the population, select older patients with end-stage liver diseases can benefit from LT, which largely restores their expected life spans.

Volumetric laser endomicroscopy in the biliary and pancreatic ducts: a feasibility study with histological correlation.

BACKGROUND: Volumetric laser endomicroscopy (VLE) provides circumferential images 3 mm into the biliary and pancreatic ducts. We aimed to correlate VLE images with the normal and abnormal microstructure of these ducts. METHODS: Samples from patients undergoing hepatic or pancreatic resection were evaluated. VLE images were collected using a low-profile VLE catheter inserted manually into the biliary and pancreatic ducts ex vivo. Histological correlation was assessed by two unblinded investigators. RESULTS: 25 patients (20 liver and 5 pancreatic samples) and 111 images were analyzed. VLE revealed three histological layers: epithelium, connective tissue, and parenchyma. It identified distinctive patterns for primary sclerosing cholangitis (PSC), pancreatic cysts, neuroendocrine tumor, and adenocarcinoma adjacent to the pancreatic duct or ampulla. VLE failed to identify dysplasia in a dominant stricture and inflammatory infiltrates in PSC. Reflectivity measurements of the liver parenchyma diagnosed liver cirrhosis with high sensitivity. CONCLUSIONS: VLE can identify histological changes in the biliary and pancreatic ducts allowing real-time diagnosis. Further studies are needed to measure the accuracy of VLE in a larger sample and to validate our findings in vivo.

Heavy Coffee Consumption and Risk of Pancreatitis: A Systematic Review and Meta-Analysis.

BACKGROUND/OBJECTIVES: Heavy consumption of coffee may have a protective effect against pancreatitis although results from previous studies were inconsistent. This meta-analysis was conducted with the aim to summarize all available data. METHODS: This meta-analysis included observational studies that compared the risk of pancreatitis between heavy coffee-drinkers and individuals who were not heavy coffee-drinkers. Pooled risk ratios (RRs) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. RESULTS: Out of 219 retrieved articles, four studies with 351,137 participants met the eligibility criteria and were included in the analysis. The risk of pancreatitis among heavy coffee-drinkers was significantly lower than individuals who were not heavy coffee-drinkers with the pooled RR of 0.78 (95% CI 0.67-0.91). The statistical heterogeneity between the studies was insignificant (I2 = 0%). CONCLUSIONS: This meta-analysis demonstrated a significantly decreased risk of pancreatitis among heavy coffee-drinkers. However, further investigations are still required to determine causality and potential clinical application.

Racial, Ethnic, and Age Disparities in Incidence and Survival of Intrahepatic Cholangiocarcinoma in the United States; 1995-2014.

INTRODUCTION AND AIM: Despite reports of increased incidence of intrahepatic cholangiocarcinoma (iCCA) in the United States, the impact of age or influences of race and ethnicity are not clear. Disparities in iCCA outcomes across various population subgroups also are not readily recognized due to the rarity of this cancer. We examined ethnic, race, age, and gender variations in iCCA incidence and survival using data from the Surveillance, Epidemiology, and End Results Program (1995-2014). MATERIAL AND METHODS: We assessed age-adjusted incidence rates, average annual percentage change in incidence, and hazard ratios (HRs) with 95% confidence intervals (CIs) for all-cause and iCCA-specific mortality. RESULTS: Overall, 11,127 cases of iCCA were identified, with an age-adjusted incidence rate of 0.92 per 100,000. The incidence rate increased twofold, from 0.49 per 100,000 in 1995 to 1.49 per 100,000 in 2014, with an average annual rate of increase of 5.49%. The iCCA incidence rate was higher among persons age 45 years or older than those younger than 45 years (1.71 vs. 0.07 per 100,000), among males than females (0.97 vs. 0.88 per 100,000) and among Hispanics than non-Hispanics (1.18 vs. 0.89 per 100,000). Compared to non-Hispanics, Hispanics had poorer 5-year allcause mortality (HR = 1.11, 95%CI: 1.05-1.19) and poorer iCCA-specific mortality (HR = 1.15, 95%CI: 1.07-1.24). Survival rates were poor also for individuals age 45 years or older, men, and Blacks and American Indians/Alaska Natives. CONCLUSION: The results demonstrate ethnic, race, age and gender disparities in iCCA incidence and survival, and confirm continued increase in iCCA incidence in the United States.

An Argument for Vitamin D, A, and Zinc Monitoring in Cirrhosis.

Malnutrition is prevalent in cirrhosis. Vitamin and mineral deficiencies, including vitamin D, vitamin A, and zinc, are common and have been shown to correlate with survival. Our aim was to review the mechanisms of vitamin D, vitamin A, and zinc deficiencies in cirrhosis and the clinical assessment of affected patients, their outcomes based on the current literature, and management. This is a narrative review including the relevant literature for cirrhosis and vitamin D, vitamin A, and zinc deficiencies. Vitamin D deficiency has important effects in cirrhosis, regardless of the cause of chronic liver disease.These effects include associations with fibrosis and outcomes such as infections, hepatocellular carcinoma, and mortality. Vitamin A deficiency is associated with liver disease progression to cirrhosis and clinical decompensation, including occurrence of ascites or hepatic encephalopathy. Zinc deficiency can lead to hepatic encephalopathy and impaired immune function. Such deficiencies correlate with patient survival and disease severity. Caution should be applied when replacing vitamin D, vitamin A, and zinc to avoid toxicity. Identification and appropriate treatment of vitamin and mineral deficiencies in cirrhosis may reduce specific nutritional and cirrhosis-related adverse events. Routine monitoring of vitamin A, vitamin D and zinc levels in cirrhosis should be considered.