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.

The Impact of COVID-19 in Gastroenterology and Hepatology.

The 2019 coronavirus disease (COVID-19), an airborne infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a global pandemic. SARS-CoV-2 relies on the angiotensin-converting enzyme 2 receptor for cellular entry and the abundance of this receptor in the gastrointestinal (GI) tract may help explain the GI manifestations, including dysgeusia, nausea, vomiting, diarrhea, and abdominal pain, present in over 40% of infected patients. GI tract involvement also raises the concern for oral-fecal transmission which is poorly understood. Outcome studies in COVID-19 patients with preexisting liver disease and inflammatory bowel disease show predominantly mild transaminase elevations and no increased risk from the use of biological agents in inflammatory bowel disease patients. High-dose corticosteroids, however, should be avoided. As endoscopic procedures are aerosol-generating, modifications to clinical practice is necessary to minimize the spread of COVID-19. We have reviewed current literature to describe the impact of COVID-19 in gastroenterology and hepatology as well as targets of future research.

Pancreatic Steatosis: An Emerging Clinical Entity.

Pancreatic steatosis is an emerging clinical entity whose pathophysiology, natural history, and long-term complications are poorly characterized in the current literature. Epidemiological and prospective studies have described prevalence rates between 16% and 35%. Although the natural history is not well known, there are strong associations with obesity, metabolic syndrome, type 2 diabetes mellitus, and nonalcoholic fatty liver disease. Ectopic fat accumulation of the pancreas can cause chronic, low-grade inflammation from adipocytokine imbalances that involve beta cells and acinar cells. This mechanism can lead to pancreatic endocrine and exocrine dysfunction and initiate carcinogenesis. Although it is associated with morbid conditions, pancreatic steatosis may be amendable to treatment with a healthy diet, less meat consumption, exercise, and smoking cessation. Pancreatic steatosis should factor into clinical decision-making and prognostication of patients with pancreatic and systemic disease. This review seeks to describe the pathophysiology, natural history, diagnosis, and complications of this emerging clinically relevant entity.

Pancreatic steatosis: an update.

PURPOSE OF REVIEW: Pancreatic steatosis is a clinical entity with emerging significance and impacts patient health in a multitude of ways. It has a high prevalence in the global population with predilections for different demographics by age, sex and ethnicity. Understanding the pathophysiology, clinical features and complications of this entity may be important to understanding the consequences of the ongoing obesity global epidemic. RECENT FINDINGS: Obesity and metabolic syndrome contribute to metabolic derangements that result in lipid mishandling by adipocytes. Adipocytokine imbalances in circulation and in the pancreatic microenvironment cause chronic, low-grade inflammation. The resulting beta cell and acinar cell apoptosis leads to pancreatic endocrine and exocrine dysfunction. Furthermore, these adipocytokines regulate cell growth, differentiation, as well as angiogenesis and lymphatic spread. These consequences of adipocyte infiltration are thought to initiate carcinogenesis, leading to pancreatic intraepithelial neoplasia and pancreatic ductal adenocarcinoma. SUMMARY: Obesity will lead to millions of deaths each year and pancreatic steatosis may be the key intermediate entity that leads to obesity-related complications. Enhancing our understanding may reveal strategies for preventing mortality and morbidity related to the global epidemic of obesity. Further research is needed to determine the pathophysiology, long-term complications and effective treatment strategies for this condition.

The Pathophysiology of Portal Hypertension.

This article reviews the pathophysiology of portal hypertension that includes multiple mechanisms internal and external to the liver. This article starts with a review of literature describing the cellular and molecular mechanisms of portal hypertension, microvascular thrombosis, sinusoidal venous congestion, portal angiogenesis, vascular hypocontractility, and hyperdynamic circulation. Mechanotransduction and the gut-liver axis, which are newer areas of research, are reviewed. Dysfunction of this axis contributes to chronic liver injury, inflammation, fibrosis, and portal hypertension. Sequelae of portal hypertension are discussed in subsequent studies.

The Disease Severity Index for Inflammatory Bowel Disease Is a Valid Instrument that Predicts Complicated Disease.

BACKGROUND: The disease severity index (DSI) for inflammatory bowel disease (IBD) combines measures of disease phenotype, inflammatory activity, and patient-reported outcomes. We aimed to validate the DSI and assess its utility in predicting a complicated IBD course. METHODS: A multicenter cohort of adults with IBD was recruited. Intraclass correlation coefficients (ICCs) and weighted Kappa assessed inter-rater reliability. Cronbach's alpha measured internal consistency of DSI items. Spearman's rank correlations compared the DSI with endoscopic indices, symptom indices, quality of life, and disability. A subgroup was followed for 24 months to assess for a complicated IBD course. Area under the receiver operating characteristics curve (AUROC) and multivariable logistic regression assessed the utility of the DSI in predicting disease progression. RESULTS: Three hundred and sixty-nine participants were included (Crohn's disease [CD], n = 230; female, n = 194; mean age, 46 years [SD, 15]; median disease duration, 11 years [interquartile range, 5-21]), of which 171 (CD, n = 99; ulcerative colitis [UC], n = 72) were followed prospectively. The DSI showed inter-rater reliability for CD (ICC 0.93, n = 65) and UC (ICC 0.97, n = 33). The DSI items demonstrated inter-rater agreement (Kappa > 0.4) and internal consistency (CD, α > 0.59; UC, α > 0.75). The DSI was significantly associated with endoscopic activity (CDn=141, r = 0.65, P < .001; UCn=105, r = 0.80, P < .001), symptoms (CDn=159, r = 0.69, P < .001; UCn=132, r = 0.58, P < .001), quality of life (CDn=198, r = -0.59, P < .001; UCn=128, r = -0.68, P < .001), and disability (CDn=83, r = -0.67, P < .001; UCn=52, r = -0.74, P < .001). A DSI of 23 best predicted a complicated IBD course (AUROC = 0.82, P < .001) and was associated with this end point on multivariable analyses (aOR, 9.20; 95% confidence interval, 3.32-25.49). CONCLUSIONS: The DSI reliably encapsulates factors contributing to disease severity and accurately prognosticates the longitudinal IBD course.

This study shows that the disease severity index (DSI) for inflammatory bowel disease (IBD) is a valid and reliable instrument encapsulating the disease phenotype, disease activity, and impact of the disease on the patient; and it accurately predicts for incident disease complications.

Alcohol Use Disorder and Alcohol-Associated Liver Disease.

This article is part of a Festschrift commemorating the 50th anniversary of the National Institute on Alcohol Abuse and Alcoholism (NIAAA). Established in 1970, first as part of the National Institute of Mental Health and later as an independent institute of the National Institutes of Health, NIAAA today is the world's largest funding agency for alcohol research. In addition to its own intramural research program, NIAAA supports the entire spectrum of innovative basic, translational, and clinical research to advance the diagnosis, prevention, and treatment of alcohol use disorder and alcohol-related problems. To celebrate the anniversary, NIAAA hosted a 2-day symposium, "Alcohol Across the Lifespan: 50 Years of Evidence-Based Diagnosis, Prevention, and Treatment Research," devoted to key topics within the field of alcohol research. This article is based on Dr. Shah's presentation at the event. NIAAA Director George F. Koob, Ph.D., serves as editor of the Festschrift.

Anorectal manometry to diagnose dyssynergic defecation: Systematic review and meta-analysis of diagnostic test accuracy.

BACKGROUND: Chronic constipation is a common condition, and dyssynergic defecation underlies up to 40% of cases. Anorectal manometry is recommended to assess for dyssynergic defecation among chronically constipated patients but remains poorly standardized. We aimed to evaluate the diagnostic accuracy of anorectal manometry and determine optimal testing parameters. METHODS: We performed a systematic review with meta-analysis of diagnostic test accuracy including cohort studies of chronically constipated patients and case-control studies of patients with dyssynergic defecation or healthy controls. Meta-analysis was performed to determine summary sensitivity, specificity, and area under the curve (AUC) with 95% confidence intervals (CI). KEY RESULTS: A total of 15 studies comprising 2140 patients were included. Including all studies (estimating optimal diagnostic accuracy), the AUC was 0.78 [95% CI 0.72-0.82], summary sensitivity was 79% [61%-90%], and summary specificity was 64% [44%-79%] to diagnose dyssynergic defecation. In cohort studies only (estimating real-world diagnostic accuracy), the AUC was 0.72 [0.66-0.77], summary sensitivity was 86% [64%-95%], and summary specificity was 49% [30%-68%]. Employing three consecutive simulated defecation attempts improved sensitivity to 94%. A fourth simulated defecation maneuver with air insufflation may improve accuracy. Measuring anorectal pressures to identify complex dyssynergic patterns did not improve real-world diagnostic accuracy estimates over anal pressure measurement alone. Choice of manometry system did not impact diagnostic accuracy. CONCLUSIONS & INFERENCES: Following the current iteration of the London consensus protocol (three simulated defecation attempts measuring anal relaxation), the role of anorectal manometry in evaluating dyssynergic defecation appears limited. Future iterations of this protocol may improve diagnostic accuracy.

Examining the clinical course of genotype 1 chronic hepatitis C patients treated with the cosmos regimen: including patients with advanced liver disease and East Asian ancestry.

BACKGROUND/OBJECTIVES: The COSMOS study was a phase 2a clinical trial that showed high cure rates of genotype 1 chronic hepatitis C (CHC) and a favorable side effect profile using a 12-week regimen of simeprevir + sofosbuvir (SIM + SOF). Given the small number of patients treated with the SIM + SOF regimen in the COSMOS trial, there is uncertainty regarding the efficacy and safety of this combination therapy. We now report our experience with the COSMOS regimen in the multiethnic population of Hawaii, including patients of East Asian ancestry and with decompensated cirrhosis. METHODS: This study is a retrospective review of 138 patients treated with a fixed dose regimen of SIM 150 mg and SOF 400 mg daily at a single referral center. We collected data on demographics, side effects, laboratory studies and sustained virological response (SVR). Statistical analysis was performed with Stata v8.2 software. RESULTS: Baseline characteristics of the 138 patients initiated with SIM + SOF therapy were: 68.8 % cirrhotic (22.1 % of those Child-Pugh Class B), 37 % Asian, 11.6 % Pacific Islander, 63 % male, mean age 61.3 ± 7.8 years, mean BMI 27.8 ± 6.1 kg/m(2), 26.8 % diabetic, 63.8 % genotype 1a, 44.9 % previously treatment experienced. A total of 100 % of patients that completed therapy (n = 137) had undetectable viral loads at end of treatment (EOT). Twelve patients relapsed post-treatment resulting in an overall 12 week SVR (SVR12) rate of 89.1 %. 95 % of decompensated cirrhotic patients achieved SVR12, compared to 85.3 % of compensated cirrhotic patients and 93 % of non-cirrhotic patients. 92 % of Asian patients achieved SVR12 compared to 87.5 % in non-Asian patients. There were no statistically significant differences in SVR12 between treatment naive and treatment experienced patients (86.8 vs 91.9 %). 87.5 % of post-transplant patients achieved SVR12. The main side effects were headache 16.2 %, fatigue 24.2 %, pruritis 14.1 %; none were >grade 2 in severity. There were no differences in side effect profiles of patients with decompensated cirrhosis. Pruritis only was statistically significant between Asians and non-Asians (22 vs 5.7 %). Trends toward improvement in platelet counts and total bilirubin were noted at 12-weeks post treatment, while improvement in albumin in cirrhotic patients reached statistical significance (3.77-4.01 mg/dL, p = 0.0108). CONCLUSIONS: The 12-week fixed dose course of SIM + SOF was well tolerated in a multiethnic population of primarily cirrhotic patients, including those with decompensated disease. This real world trial achieved SVR12 rates comparable to the COSMOS data. Higher incidence of adverse side effects was not observed with an exception of higher rate of pruritis in Asians. The increase in albumin in cirrhotic patients was statistically significant and suggested early improvement in synthetic function following viral eradication. Higher BMI (≥30 kg/m(2)) was the only factor that correlated with post-treatment relapse by multivariate analysis.